CROSS REFERENCE TO RELATED APPLICATIONS

This application claims the benefit of priority of United States Provisional Application No. 62/090,880, filed December 1 1 , 2014, the entire contents of which is incorporated herein by reference.

FIELD

The present disclosure relates generally to anti-C10orf54 antibodies, including antibody-drug conjugates comprising the antibodies, and methods of their use.

BACKGROUND

C10orf54 is a single-pass type I transmembrane protein that is 31 1 amino acids in length and includes a signal sequence and one IgV-like domain in its intracellular region. It is potentially a member of the B7 family of proteins and it has approximately 24% sequence identity to B7-H1 /PD-L1 (Flajnik et al. , Immunogenetic 64:571 -590 (2012)). The mouse ortholog to C10orf54 is known as V-region |mmunoglobulin-containing Suppressor of T Cell Activation (VISTA; also known as PD-L3). VISTA was cloned from a library of CD4 positive regulatory T cells (Treg) (Wang et al. , JEM 208(3):577-592 (201 1 )). VISTA is primarily expressed on hematopoietic cells, and VISTA expression is highly regulated on myeloid antigen-presenting cells (APCs) and T cells (Wang et al. , supra).

VISTA appears to have functional activities that are nonredundant with other Ig superfamily members and may play a role in the development of autoimmunity and immune surveillance in cancer. For example, expression of a VISTA-lg fusion protein has been shown to inhibit T cell proliferation and cytokine production in vitro and overexpression of VISTA on MCA105 tumor cells interferes with a host's protective antitumor immunity (Wang et al. , supra). Moreover, administration of a VISTA-specific monoclonal antibody enhanced CD4 positive T cell response in vivo and the development of autoimmunity (Wang et al. , supra). Monoclonal antibodies against C10orf54 have also been shown to prevent acute graft-versus-host disease in mice (Flies et al. , J. Immunology 187(4): 1537-1541 (201 1 )).

Citation or discussion of a reference herein shall not be construed as an admission that such is prior art to the present disclosure.

SUMMARY

The present disclosure provides antibodies that bind C10orf54, including humanized antibodies and antibody-drug conjugates comprising the humanized antibodies, and methods of use of the antibodies and the antibody-drug conjugates, including for the diagnosis and treatment of cancers. The present disclosure further provides proteins that bind to C10orf54, including binding proteins, such as antibodies, that bind to one or more C10orf54 proteins or chimeric proteins. Such binding proteins, including antibodies, may be antagonists (e.g. , inhibit one or more of the biological activities of C10orf54).

In a first aspect, provided herein are antibodies that bind to C10orf54, including a C10orf54 polypeptide, a C10orf54 polypeptide fragment or a C10orf54 epitope, collectively referred to herein as anti-C10orf54 antibodies. Also provided herein are anti-C10orf54 antibodies that are conjugated to drugs as antibody-drug conjugates (ADCs), including ADCs of the formula A-L-CTX, wherein A is an antibody, L is a linker, and CTX is cytotoxin. In some embodiments the anti-C10orf54 antibodies are humanized antibodies that bind to a C10orf54 polypeptide, a C10orf54 polypeptide fragment or a C10orf54 epitope. In certain embodiments, the anti-C10orf54 antibody comprises a VH domain, VL domain, VH CDR1 , VH CDR2, VH CDR3, VL CDR1 , VL CDR2, and/or VL CDR3 of monoclonal antibody 5B, 46A, 97A, 128A, 146C, 208A, 215A, 26A, 164A, 230A, 76E1 , 53A, 259A, 33A, 39A, 124A, 175A, 321 D, 141 A, 51 A, 353A, or 305A described herein (e.g. , Tables 12-33), or a humanized variant thereof. In certain embodiments, the anti-C10orf54 antibody can further comprise a VH FR1 , VH FR2, VH FR3, VH FR4, VL FR1 , VL FR2, VL FR3, and/or VL FR4 of a human germline immunoglobulin amino acid sequence or a variant thereof.

In certain embodiments, the antibody comprises less than six CDRs. In some embodiments, the antibody comprises or consists of one, two, three, four, or five CDRs selected from the group consisting of VH CDR1 , VH CDR2, VH CDR3, VL CDR1 , VL CDR2, and/or VL CDR3. In specific embodiments, the antibody comprises or consists of one, two, three, four, or five CDRs selected from the group consisting of VH CDR1 , VH CDR2, VH CDR3, VL CDR1 , VL CDR2, and/or VL CDR3 of the monoclonal antibody 5B, 46A, 97A, 128A, 146C, 208A, 215A, 26A, 164A, 230A, 76E1 , 53A, 259A, 33A, 39A, 124A, 175A, 321 D, 141 A, 51A, 353A, or 305A described herein {e.g., Tables 12-33), or a humanized variant thereof. In specific embodiments, the antibody further comprises a VH FR1 , VH FR2, VH FR3, VH FR4, VL FR1 , VL FR2, VL FR3, and/or VL FR4 of a human germline immunoglobulin amino acid sequence or a variant thereof.

In specific embodiments, the antibody is a humanized antibody, a monoclonal antibody, a recombinant antibody, an antigen binding fragment or any combination thereof. In particular embodiments, the antibody is a humanized monoclonal antibody as described herein (e.g. , 5B, 46A, 97A, 128A, 146C, 208A, 215A, 26A, 164A, 230A, 76E1 , 53A, 259A, 33A, 39A, 124A, 175A, 321 D, 141 A, 51 A, 353A, or 305A described herein (e.g., Tables 12-33) with a VH domain, VL domain, VH CDR1 , VH CDR2, VH CDR3, VL CDR1 , VL CDR2, and/or VL CDR3), or antigen binding fragment thereof, that binds to a C10orf54 polypeptide (e.g., a cell surface-expressed or soluble C10orf54), a C10orf54 fragment, or a C10orf54 epitope.

In a second aspect, provided herein are antibodies, including humanized antibodies,

(i) that competitively block (e.g., in a dose-dependent manner) an anti-C10orf54 antibody provided herein from binding to a C10orf54 polypeptide (e.g., a cell surface-expressed or soluble C10orf54), a C10orf54 fragment, or a C10orf54 epitope and/or

(ii) that bind to a C10orf54 epitope that is bound by an anti-C10orf54 antibody (e.g., humanized anti-C10orf54 antibodies) provided herein. In other embodiments, the antibody competitively blocks (e.g., in a dose-dependent manner) monoclonal antibody 5B, 46A, 97A, 128A, 146C, 208A, 215A, 26A, 164A, 230A, 76E1 , 53A, 259A, 33A, 39A, 124A, 175A, 321 D, 141 A, 51 A, 353A, or 305A described herein (e.g., Tables 12-33)or a humanized variant thereof from binding to a C10orf54 polypeptide (e.g., a cell surface-expressed or soluble C10orf54), a C10orf54 fragment, or a C10orf54 epitope. In other embodiments, the antibody binds to a C10orf54 epitope that is bound (e.g., recognized) by monoclonal antibody 5B, 46A, 97A, 128A, 146C, 208A, 215A, 26A, 164A, 230A, 76E1 , 53A, 259A, 33A, 39A, 124A, 175A, 321 D, 141 A, 51 A, 353A, or 305A described herein (e.g., Tables 12-33) or a humanized variant thereof (e.g. humanized anti-C10orf54 antibodies).

In certain embodiments, the anti-C10orf54 antibodies (e.g. , humanized anti-C10orf54 antibodies) provided herein (e.g. , 5B, 46A, 97A, 128A, 146C, 208A, 215A, 26A, 164A, 230A, 76E1 , 53A, 259A, 33A, 39A, 124A, 175A, 321 D, 141 A, 51 A, 353A, or 305A described herein (e.g. , Tables 12-33) with a VH domain, VL domain, VH CDR1 , VH CDR2, VH CDR3, VL CDR1 , VL CDR2, and/or VL CDR3) are conjugated or recombinantly fused to a diagnostic agent, detectable agent or therapeutic agent. In some aspects, the therapeutic agent is a chemotherapeutic agent {e.g., a cystotoxic agent such as cytotoxin). In some aspects, the detectable agent is a radioisotope, an enzyme, a fluorescent compound, a bioluminescent compound or a

chemiluminescent compound. In certain embodiments, the anti-C10orf54 antibodies provided herein (e.g. , 5B, 46A, 97A, 128A, 146C, 208A, 215A, 26A, 164A, 230A, 76E1 , 53A, 259A, 33A, 39A, 124A, 175A, 321 D, 141 A, 51 A, 353A, or 305A described herein (e.g. , Tables 12-33) with a VH domain, VL domain, VH CDR1 , VH CDR2, VH CDR3, VL CDR1 , VL CDR2, and/or VL CDR3) are conjugated to drugs as antibody-drug conjugates (ADCs). In some aspects, the antibody-drug conjugate (ADC) is of the formula A-L-CTX, wherein A is an antibody, L is a linker, and CTX is a cytotoxin.

In certain embodiments, provided are compositions comprising an anti-C10orf54 antibody (e.g. , humanized anti-C10orf54 antibodies) described herein. In some embodiments, the compositions comprise an antibody-drug conjugate wherein the antibody is an anti-C10orf54 antibody provided herein (e.g. , 5B, 46A, 97A, 128A, 146C, 208A, 215A, 26A, 164A, 230A, 76E1 , 53A, 259A, 33A, 39A, 124A, 175A, 321 D, 141 A, 51 A, 353A, or 305A described herein (e.g. , Tables 12-33) with a VH domain, VL domain, VH CDR1 , VH CDR2, VH CDR3, VL CDR1 , VL CDR2, and/or VL CDR3). Also provided herein are pharmaceutical compositions comprising an anti-C10orf54 antibody, including a humanized anti-C10orf54 antibody, provided herein (e.g. , 5B, 46A, 97A, 128A, 146C, 208A, 215A, 26A, 164A, 230A, 76E1 , 53A, 259A, 33A, 39A, 124A, 175A, 321 D, 141 A, 51 A, 353A, or 305A described herein (e.g. , Tables 12-33) with a VH domain, VL domain, VH CDR1 , VH CDR2, VH CDR3, VL CDR1 , VL CDR2, and/or VL CDR3).

In certain embodiments, the antibody provided herein binds to a first group of

C10orf54 proteins or chimeric proteins designated CC1 (SEQ ID NO: 1079), CC4 (SEQ ID NO: 1245), CC5 (SEQ ID NO: 1246), CC8 (SEQ ID NO: 1249), and CC10 (SEQ ID NO: 1251 ), and does not bind to a second groupd of C10orf54 proteins or chimeric proteins designated CC2 (SEQ ID NO: 1243), CC3 (SEQ ID NO: 1244), CC6 (SEQ ID NO: 1247), CC7 (SEQ ID NO: 1248), and CC9 (SEQ ID NO: 1250).

In certain embodiments, the antibody provided herein binds a first group of C10orf54 proteins or chimeric proteins designated CC1 (SEQ ID NO: 1079), CC4 (SEQ ID NO: 1245), CC5 (SEQ ID NO: 1246), and CC8 (SEQ ID NO: 1249), and does not bind to a second groupd of C10orf54 proteins or chimeric proteins designated CC2 (SEQ ID NO: 1243), CC3 (SEQ ID NO: 1244), CC6 (SEQ ID NO: 1247), CC7 (SEQ ID NO: 1248), CC9 (SEQ ID NO: 1250), and CC10 (SEQ ID NO: 1251). In some aspected, such an antibody does not comprise one or more CDR sequences selected from the group consisting of 30, 1099, 1104, 1105, 1110, 31, 1100, 1106, 1111, 1116, 32, 1101, 1107, 1112, 45, 1102, 1108, 1113, 40, 1103, 1114, 41, 1109, and 1115.

In certain embodiments, the antibody provided herein binds to a first group of

C10orf54 proteins or chimeric proteins designated CC1 (SEQ ID NO: 1079), CC4 (SEQ ID NO: 1245), and CC5 (SEQ ID NO: 1246), and does not bind to a second groupd of C10orf54 proteins or chimeric proteins designated (SEQ ID NO: 1243), CC3 (SEQ ID NO: 1244), CC6 (SEQ ID NO: 1247), CC7 (SEQ ID NO: 1248), CC8 (SEQ ID NO: 1249), CC9 (SEQ ID NO: 1250), and CC10 (SEQ ID NO: 1251). In some aspects, such an antibody does not comprise one or more CDR sequences selected from the group consisting of 36, 1081, 1086, 1087, 1092, 37, 1082, 1088, 1093, 1098, 38, 1083, 1089, 1094, 45, 1084, 1090, 1095, 46, 1085, 1096, 47, 1091, and 1097.

In certain embodiments, the antibody provided herein binds to a first group of

C10orf54 proteins or chimeric proteins designated CC1 (SEQ ID NO: 1079), CC4 (SEQ ID NO: 1245), CC5 (SEQ ID NO: 1246), CC8 (SEQ ID NO: 1249), and CC9 (SEQ ID NO: 1250), and does not bind to a second groupd of C10orf54 proteins or chimeric proteins designated CC2 (SEQ ID NO: 1243), CC3 (SEQ ID NO: 1244), CC6 (SEQ ID NO: 1247), CC7 (SEQ ID NO: 1248), CC9 (SEQ ID NO: 1250), and CC10 (SEQ ID NO: 1251). In some aspects, such an antiobdy does not comprise one or more CDR sequences selected from the group consisting of 33, 1117, 1122, 1123, 1128, 34, 1118, 1124, 1129, 1134, 35, 1119, 1125, 1130, 42, 1120, 1126, 1131, 43, 1121, 1132, 44, 1127, and 1133.

In certain embodiments, the antibody provided herein binds to a first group of

C10orf54 proteins or chimeric proteins designated CC1 (SEQ ID NO: 1079), CC3 (SEQ ID NO: 1244), CC4 (SEQ ID NO: 1245), CC5 (SEQ ID NO: 1246), CC8 (SEQ ID NO: 1249), and CC9 (SEQ ID NO: 1250), and does not bind to a second groupd of C10orf54 proteins or chimeric proteins designated CC2 (SEQ ID NO: 1243), CC6 (SEQ ID NO: 1247), CC7 (SEQ ID NO: 1248), and CC10 (SEQ ID NO: 1251 ).

In certain embodiments, the antibody provided herein binds to a first group of

C10orf54 proteins or chimeric proteins designated CC1 (SEQ ID NO: 1079), CC4 (SEQ ID NO: 1245), CC5 (SEQ ID NO: 1246), CC8 (SEQ ID NO: 1249), and CC10 (SEQ ID NO: 1251 ), and does not bind to a second groupd of C10orf54 proteins or chimeric proteins designated CC2 (SEQ ID NO: 1243), CC3 (SEQ ID NO: 1244), CC6 (SEQ ID NO: 1247), CC7 (SEQ ID NO: 1248), CC9 (SEQ ID NO: 1250), and CC10 (SEQ ID NO: 1251 ).

In a third aspect, provided are isolated nucleic acid molecules encoding a VH chain, VL chain, VH domain, VL domain, VH CDR1 , VH CDR2, VH CDR3, VL CDR1 , VL CDR2, and/or VL CDR3 of anti-C10orf54 antibodies as described herein (e.g. , 5B, 46A, 97A, 128A, 146C, 208A, 215A, 26A, 164A, 230A, 76E1 , 53A, 259A, 33A, 39A, 124A, 175A, 321 D, 141 A, 51 A, 353A, or 305A described herein (e.g. , Tables 12-33) with a VH domain, VL domain, VH CDR1 , VH CDR2, VH CDR3, VL CDR1 , VL CDR2, and/or VL CDR3), including humanized anti-C10orf54 antibodies, that bind to a C10orf54 polypeptide, a C10orf54 polypeptide fragment, or a C10orf54 epitope. In certain embodiments, the nucleic acid molecule encodes a VH domain, VL domain, VH CDR1 , VH CDR2, VH CDR3, VL CDR1 , VL CDR2, and/or VL CDR3 of

monoclonal antibody 5B, 46A, 97A, 128A, 146C, 208A, 215A, 26A, 164A, 230A, 76E1 , 53A, 259A, 33A, 39A, 124A, 175A, 321 D, 141 A, 51A, 353A, or 305A described herein (e.g. , Tables 12-33), or a humanized variant thereof. In certain embodiments, the nucleic acid molecule further encodes a VH FR1 , VH FR2, VH FR3, VH FR4, VL FR1 , VL FR2, VL FR3, and/or VL FR4 of a human germline immunoglobulin amino acid sequence or a variant thereof. Also provided herein are vectors and host cells comprising the nucleic acid molecules encoding an anti-C10orf54 antibody (e.g. , humanized anti-C10orf54 antibodies), as well as methods of producing an anti-C10orf54 antibody by culturing the host cells provided herein under conditions that promote the production of the anti-C10orf54 antibody.

In a fourth aspect, provided herein are methods of treating, preventing or alleviating a disease, disorder or condition, including one or more symptoms of a disease, disorder or condition, comprising administering a therapeutically effective amount of an anti-C10orf54 antibody as described herein (e.g., 5B, 46A, 97A, 128A, 146C, 208A, 215A, 26A, 164A, 230A, 76E1 , 53A, 259A, 33A, 39A, 124A, 175A, 321 D, 141 A, 51 A, 353A, or 305A described herein (e.g. , Tables 12-33) with a VH domain, VL domain, VH CDR1 , VH CDR2, VH CDR3, VL CDR1 , VL CDR2, and/or VL CDR3), including an antibody-drug conjugate (ADC) comprising an anti-C10orf54 antibody, provided herein (e.g. , 5B, 46A, 97A, 128A, 146C, 208A, 215A, 26A, 164A, 230A, 76E1 , 53A, 259A, 33A, 39A, 124A, 175A, 321 D, 141 A, 51A, 353A, or 305A described herein (e.g. , Tables 12-33) with a VH domain, VL domain, VH CDR1 , VH CDR2, VH CDR3, VL CDR1 , VL CDR2, and/or VL CDR3) to a subject, thereby treating, preventing or alleviating the disease, disorder or condition, including one or more symptoms of the disease, disorder or condition. In some embodiments the anti-C10orf54 antibodies are humanized antibodies that bind to a C10orf54 polypeptide, a C10orf54

polypeptide fragment or a C10orf54 epitope. In one embodiment, the disease, disorder or condition is caused by or otherwise associated with C10orf54, including by or associated with C10orf54-expressing cells (e.g. , tumor cells, myeloid-derived suppressor cells (MDSC), suppressive dendritic cells (suppressive DC), and /or regulatory T cells (T regs)). In certain embodiments, the disease is a cancer, such as a leukemia, a bladder cancer, a skin cancer, a colon cancer, a breast cancer, a liver cancer, a kidney cancer, a lung cancer, a stomach cancer, a pancreas cancer, an esophagus cancer or a fibrosarcoma. In one embodiment, the leukemia is an acute myeloid leukemia (AML). In other embodiments, the disease is graft-versus-host disease (GVHD). Additional methods provided include using an anti-C10orf54 antibody with C10orf54 binding activity for C10orf54-expressing cells, provided herein (e.g. , 5B, 46A, 97A, 128A, 146C, 208A, 215A, 26A, 164A, 230A, 76E1 , 53A, 259A, 33A, 39A, 124A, 175A, 321 D, 141 A, 51 A, 353A, or 305A described herein (e.g. , Tables 12-33) with a VH domain, VL domain, VH CDR1 , VH CDR2, VH CDR3, VL CDR1 , VL CDR2, and/or VL CDR3), for example, as an unconjugated antibody or conjugated antibody (ADC), including to inhibit and/or kill the C10orf54-expressing cells (e.g. , with anti-tumor activity to mediate an anti-tumor effect). In certain embodiments, the anti-C10orf54 antibodies, including ADCs comprising the anti-C10orf54 antibodies, provided herein (e.g. , 5B, 46A, 97A, 128A, 146C, 208A, 215A,

26A, 164A, 230A, 76E1 , 53A, 259A, 33A, 39A, 124A, 175A, 321 D, 141 A, 51 A, 353A, or 305A described herein {e.g. , Tables 12-33) with a VH domain, VL domain, VH CDR1 , VH CDR2, VH CDR3, VL CDR1 , VL CDR2, and/or VL CDR3) inhibit

C10orf54-mediated suppressor activity on T cells (e.g. , to allow an effective anti-tumor immune response). In certain embodiments, the anti-C10orf54 antibodies provided herein (e.g. , 5B, 46A, 97A, 128A, 146C, 208A, 215A, 26A, 164A, 230A, 76E1 , 53A, 259A, 33A, 39A, 124A, 175A, 321 D, 141 A, 51 A, 353A, or 305A described herein (e.g. , Tables 12-33) with a VH domain, VL domain, VH CDR1 , VH CDR2, VH CDR3, VL CDR1 , VL CDR2, and/or VL CDR3) directly kill C10orf54-expressing cells (e.g. , C10orf54-bearing tumor cells, myeloid-derived suppressor cells (MDSC), suppressive dendritic cells (suppressive DC), and /or regulatory T cells (T regs)), for example, via antibody-dependent cellular cytotoxicity (ADCC) and/or complement-dependent cytotoxicity (CDC) In certain embodiments, antibody drug conjugates (ADCs) comprising anti-C10orf54 antibodies provided herein (e.g. , 5B, 46A, 97A, 128A, 146C, 208A, 215A, 26A, 164A, 230A, 76E1 , 53A, 259A, 33A, 39A, 124A,

175A, 321 D, 141 A, 51 A, 353A, or 305A described herein (e.g. , Tables 12-33) with a VH domain, VL domain, VH CDR1 , VH CDR2, VH CDR3, VL CDR1 , VL CDR2, and/or VL CDR3) directly kill C10orf54-expressing cells including by binding to cells expressing C10orf54 (e.g. , tumor cells, myeloid-derived suppressor cells (MDSC), suppressive dendritic cells (suppressive DC), and/or regulatory T cells (T regs)), for example, by allowing internalization of the cytotoxic drug. In certain embodiments, the anti-C10orf54 antibodies provided herein or antibody drug conjugates (ADCs) comprising anti-C10orf54 antibodies provided herein are used in methods for treating cancers (e.g. , bladder, breast, colon, connective tissue, rectal, gastric, esophageal, lung, laryx, kidney, oral, ovarian, or prostate cancer, or a sarcoma, melanoma, glioma, lymphoma or leukemia) or tumors associated with myeloid-derived suppressor cells (MDSC) (e.g. , colon carcinoma, mammary carcinoma,

fibrosarcoma, thymoma, lung carcinoma, renal cell carcinoma, mesothelioma, glioma, lymphoma, sarcoma, prostate carcinoma, sarcoma, or head and neck carcinoma). In any of the above embodiments, the anti-C10orf54 antibody can be a humanized anti-C10orf54 antibody provided herein (e.g. , 5B, 46A, 97A, 128A, 146C, 208A, 215A, 26A, 164A, 230A, 76E1 , 53A, 259A, 33A, 39A, 124A, 175A, 321 D, 141 A, 51 A, 353A, or 305A described herein (e.g. , Tables 12-33) with a VH domain, VL domain, VH CDR1 , VH CDR2, VH CDR3, VL CDR1 , VL CDR2, and/or VL CDR3)

that binds to a C10orf54 polypeptide, a C10orf54 polypeptide fragment or a C10orf54 epitope.

In a fifth aspect, provided herein are methods of inhibiting the growth of cells and/or killing cells having cell surface expression of C10orf54 comprising contacting the cells with an effective amount of an anti-C10orf54 antibody or antibody-drug conjugates comprising the anti-C10orf54 antibody provided herein (e.g. , 5B, 46A, 97A, 128A, 146C, 208A, 215A, 26A, 164A, 230A, 76E1 , 53A, 259A, 33A, 39A, 124A, 175A, 321 D, 141 A, 51 A, 353A, or 305A described herein (e.g. , Tables 12-33) with a VH domain, VL domain, VH CDR1 , VH CDR2, VH CDR3, VL CDR1 , VL CDR2, and/or VL CDR3). In one embodiment, the cell is a regulatory T cell (e.g. , a CD4+ Foxp3+ regulatory T cell). In certain embodiments, provided herein is a method of inhibiting the growth of a tumor with inflammation in a subject comprising administering an effective amount of the anti-C10orf54 antibodies, including ADCs comprising the anti-C10orf54 antibodies, provided herein (e.g. , 5B, 46A, 97A, 128A, 146C, 208A, 215A, 26A, 164A, 230A, 76E1 , 53A, 259A, 33A, 39A, 124A, 175A, 321 D, 141 A, 51 A, 353A, or 305A described herein (e.g. , Tables 12-33) with a VH domain, VL domain, VH CDR1 , VH CDR2, VH CDR3, VL CDR1 , VL CDR2, and/or VL CDR3). In other embodiments, the cell is a myeloid-derived suppressor cell (e.g. , a CD1 1 b+ or

CD1 1 bhigh myeloid-derived suppressor cell) or a suppressive dendritic cell (e.g. , a

CD1 1 b+ or CD1 1 bhigh dendritic cell).. In other embodiments, the cell is a cancerous or pre-cancerous cell. Additional methods provided include using an anti-C10orf54 antibody with C10orf54 binding activity for C10orf54-expressing cells provided herein (e.g. , 5B, 46A, 97A, 128A, 146C, 208A, 215A, 26A, 164A, 230A, 76E1 , 53A, 259A, 33A, 39A, 124A, 175A, 321 D, 141 A, 51 A, 353A, or 305A described herein (e.g. , Tables 12-33) with a VH domain, VL domain, VH CDR1 , VH CDR2, VH CDR3, VL CDR1 , VL CDR2, and/or VL CDR3), for example, as an unconjugated antibody or conjugated antibody (ADC) including to inhibit and/or kill C10orf54-expressing cells (e.g. , with anti-tumor activity to mediate an anti-tumor effect). In certain

embodiments, the anti-C10orf54 antibodies, including ADCs comprising the anti-C10orf54 antibodies, provided herein (e.g. , 5B, 46A, 97A, 128A, 146C, 208A, 215A, 26A, 164A, 230A, 76E1 , 53A, 259A, 33A, 39A, 124A, 175A, 321 D, 141 A, 51 A, 353A, or 305A described herein (e.g. , Tables 12-33) with a VH domain, VL domain, VH CDR1 , VH CDR2, VH CDR3, VL CDR1 , VL CDR2, and/or VL CDR3) inhibit

C10orf54-mediated suppressor activity on T cells {e.g., to allow an effective antitumor immune response). In certain embodiments, the anti-C10orf54 antibodies provided herein (e.g., 5B, 46A, 97A, 128A, 146C, 208A, 215A, 26A, 164A, 230A, 76E1 , 53A, 259A, 33A, 39A, 124A, 175A, 321 D, 141 A, 51 A, 353A, or 305A described herein (e.g., Tables 12-33) with a VH domain, VL domain, VH CDR1 , VH CDR2, VH CDR3, VL CDR1 , VL CDR2, and/or VL CDR3) directly kill C10orf54-expressing cells (e.g., C10orf54-bearing tumor cells, myeloid-derived suppressor cells (MDSC), suppressive dendritic cells (suppressive DC), and /or regulatory T cells (T regs)), for example, via antibody-dependent cellular cytotoxicity (ADCC) and/or complement-dependent cytotoxicity (CDC) In certain embodiments, antibody drug conjugates (ADCs) comprising anti-C10orf54 antibodies provided herein (e.g., 5B, 46A, 97A, 128A, 146C, 208A, 215A, 26A, 164A, 230A, 76E1 , 53A, 259A, 33A, 39A, 124A, 175A, 321 D, 141 A, 51 A, 353A, or 305A described herein (e.g., Tables 12-33) with a VH domain, VL domain, VH CDR1 , VH CDR2, VH CDR3, VL CDR1 , VL CDR2, and/or VL CDR3) directly kill C10orf54-expressing cells including by binding to cells expressing C10orf54 (e.g. , tumor cells, myeloid-derived suppressor cells (MDSC), suppressive dendritic cells (suppressive DC), and/or regulatory T cells (T regs)), for example, by allowing internalization of the cytotoxic drug. In any of the above embodiments, the anti-C10orf54 antibody can be a humanized anti-C10orf54 antibody provided herein (e.g., 5B, 46A, 97A, 128A, 146C, 208A, 215A, 26A, 164A, 230A, 76E1 , 53A, 259A, 33A, 39A, 124A, 175A, 321 D, 141 A, 51 A, 353A, or 305A described herein (e.g., Tables 12-33) with a VH domain, VL domain, VH CDR1 , VH CDR2, VH CDR3, VL CDR1 , VL CDR2, and/or VL CDR3) that binds to a C10orf54 polypeptide, a C10orf54 polypeptide fragment or a C10orf54 epitope.

In a sixth aspect, provided herein are methods of modulating an immune response in a subject comprising administering an effective amount of an anti-C10orf54 antibody (e.g., a humanized anti-C10orf54 antibody) provided herein (e.g. , 5B, 46A, 97A, 128A, 146C, 208A, 215A, 26A, 164A, 230A, 76E1 , 53A, 259A, 33A, 39A, 124A, 175A, 321 D, 141 A, 51 A, 353A, or 305A described herein (e.g., Tables 12-33) with a VH domain, VL domain, VH CDR1 , VH CDR2, VH CDR3, VL CDR1 , VL CDR2, and/or VL CDR3) to a subject. In one embodiment, the modulating comprises increasing T cell activation. In other embodiment, the modulating comprises

increasing T cell proliferation. In another embodiment, the modulating comprises increasing cytokine production.

In a seventh aspect, provided herein are methods for detecting C10orf54 in a sample comprising contacting the sample with an anti-C10orf54 antibody (e.g. , a humanized anti-C10orf54 antibody) provided herein (e.g. , 5B, 46A, 97A, 128A, 146C, 208A,

215A, 26A, 164A, 230A, 76E1 , 53A, 259A, 33A, 39A, 124A, 175A, 321 D, 141 A, 51 A, 353A, or 305A described herein (e.g. , Tables 12-33) with a VH domain, VL domain, VH CDR1 , VH CDR2, VH CDR3, VL CDR1 , VL CDR2, and/or VL CDR3), such as an antibody that comprises a detectible agent. In certain embodiments, the sample comprises a cell expressing C10orf54 on its surface.

In an eighth aspect, provided herein are methods of treating cancers comprising administering to a subject an anti-C10orf54 antibody (e.g. , a humanized anti-C10orf54 antibody) or an antibody-drug conjugate (ADC) comprising the anti-C10orf54 antibody {e.g., an ADC of the formula A-L-CTX, wherein A is the antibody, L is a linker, and CTX is a cytotoxic agent) provided herein (e.g. , 5B, 46A, 97A, 128A, 146C, 208A, 215A, 26A, 164A, 230A, 76E1 , 53A, 259A, 33A, 39A, 124A, 175A, 321 D, 141 A, 51 A, 353A, or 305A described herein (e.g. , Tables 12-33) with a VH domain, VL domain, VH CDR1 , VH CDR2, VH CDR3, VL CDR1 , VL CDR2, and/or VL CDR3) in a therapeutically effective amount, including in an amount effective to kill a C10orf54-expressing cell (e.g. , tumor cell, myeloid-derived suppressor cell (MDSC), suppressive dendritic cell (suppressive DC), and /or regulatory T cell (T reg)). In some embodiments the cancer is acute myeloid leukemia (AML). In any of the above embodiments, the anti-C10orf54 antibody can be a humanized anti-C10orf54 antibody provided herein (e.g. , 5B, 46A, 97A, 128A, 146C, 208A, 215A, 26A, 164A, 230A, 76E1 , 53A, 259A, 33A, 39A, 124A, 175A, 321 D, 141 A, 51 A, 353A, or 305A described herein (e.g. , Tables 12-33) with a VH domain, VL domain, VH CDR1 , VH CDR2, VH CDR3, VL CDR1 , VL CDR2, and/or VL CDR3) that binds to a C10orf54 polypeptide, a C10orf54 polypeptide fragment or a C10orf54 epitope.

In a ninth aspect, provided herein are methods of killing C10orf54-expressing cells (e.g. , tumor cells, myeloid-derived suppressor cells (MDSC), suppressive dendritic cells (suppressive DC), and /or regulatory T cells (T reg)) comprising contacting a C10orf54-expressing cell (e.g. , tumor cell, myeloid-derived suppressor cell (MDSC), suppressive dendritic cell (suppressive DC), and /or regulatory T cell (T regs)) with an amount of an anti-C10orf54 antibody or an antibody-drug conjugate (ADC) comprising an anti-C10orf54 antibody {e.g., an ADC of the formula A-L-CTX, wherein A is the antibody, L is a linker, and CTX is a cytotoxic agent) provided herein (e.g. , 5B, 46A, 97A, 128A, 146C, 208A, 215A, 26A, 164A, 230A, 76E1 , 53A, 259A, 33A, 39A, 124A, 175A, 321 D, 141 A, 51 A, 353A, or 305A described herein (e.g. , Tables 12-33) with a VH domain, VL domain, VH CDR1 , VH CDR2, VH CDR3, VL CDR1 , VL CDR2, and/or VL CDR3) effective to kill the cell (e.g. , tumor cell, myeloid-derived suppressor cell (MDSC), suppressive dendritic cell (suppressive DC), and /or regulatory T cell (T reg)). In some embodiments, the tumor cell is an AML cell. In any of the above embodiments, the anti-C10orf54 antibody can be a humanized anti-C10orf54 antibody provided herein (e.g. , 5B, 46A, 97A, 128A, 146C, 208A, 215A, 26A, 164A, 230A, 76E1 , 53A, 259A, 33A, 39A, 124A, 175A, 321 D, 141 A, 51 A, 353A, or 305A described herein (e.g. , Tables 12-33) with a VH domain, VL domain, VH CDR1 , VH CDR2, VH CDR3, VL CDR1 , VL CDR2, and/or VL CDR3) that binds to a C10orf54 polypeptide, a C10orf54 polypeptide fragment or a C10orf54 epitope.

In a tenth aspect, provided herein is a kit comprising an anti-C10orf54 antibody (e.g. , a humanized anti-C10orf54 antibody) that binds to a C10orf54 polypeptide, a

C10orf54 polypeptide fragment, or a C10orf54 epitope provided herein (e.g. , 5B, 46A, 97A, 128A, 146C, 208A, 215A, 26A, 164A, 230A, 76E1 , 53A, 259A, 33A, 39A, 124A, 175A, 321 D, 141 A, 51 A, 353A, or 305A described herein (e.g. , Tables 12-33) with a VH domain, VL domain, VH CDR1 , VH CDR2, VH CDR3, VL CDR1 , VL CDR2, and/or VL CDR3). In some embodiments, the kits comprise an antibody-drug conjugate (ADC) wherein the antibody is an anti-C10orf54 antibody (e.g. , a

humanized anti-C10orf54 antibody) provided herein (e.g. , 5B, 46A, 97A, 128A, 146C, 208A, 215A, 26A, 164A, 230A, 76E1 , 53A, 259A, 33A, 39A, 124A, 175A, 321 D, 141 A, 51 A, 353A, or 305A described herein (e.g. , Tables 12-33) with a VH domain, VL domain, VH CDR1 , VH CDR2, VH CDR3, VL CDR1 , VL CDR2, and/or VL CDR3).

TERMINOLOGY

Unless defined otherwise, all technical and scientific terms used herein have the same meaning as is commonly understood by one of ordinary skill in the art. All patents, applications, published applications and other publications are incorporated by reference in their entirety. In the event that there are a plurality of definitions for a term herein, those in this section prevail unless stated otherwise.

The term "about" or "approximately" means within 20%, such as within 10%, or within 5% (or 1 % or less) of a given value or range.

As used herein, "administer" or "administration" refers to the act of injecting or otherwise physically delivering a substance as it exists outside the body {e.g., an anti-C10orf54 antibody provided herein) into a patient, such as by mucosal, intradermal, intravenous, intramuscular delivery and/or any other method of physical delivery described herein or known in the art. When a disease, or a symptom thereof, is being treated, administration of the substance typically occurs after the onset of the disease or symptoms thereof. When a disease, or symptoms thereof, are being prevented, administration of the substance typically occurs before the onset of the disease or symptoms thereof.

As used herein, an "agonist" of C10orf54 refers to a molecule that is capable of activating or otherwise increasing one or more of the biological activities of C10orf54, such as in a cell expressing C10orf54 or in a cell expressing a C10orf54 ligand, such as a C10orf54 receptor. In some embodiments, an agonist of C10orf54 {e.g., an agonistic antibody provided herein) may, for example, act by activating or otherwise increasing the activation and/or cell signaling pathways of the cell expressing a C10orf54 or a C10orf54 receptor, thereby increasing a C10orf54-mediated biological activity of the cell the relative to the C10orf54-mediated biological activity in the absence of agonist. In certain embodiments the antibodies provided herein are agonistic anti-C10orf54 antibodies.

The term "alkyl," as used herein, means a straight, branched chain, or cyclic (in this case, it would also be known as "cycloalkyl") hydrocarbon containing from 1 -10 carbon atoms. Examples of alkyl include, but are not limited to, methyl, ethyl, n-propyl, iso-propyl, n-butyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, neopentyl, n-hexyl, 3-methylhexyl, 2,2-dimethylpentyl, 2,3-dimethylhexyl, n-heptyl, n-octyl, n-nonyl, and n-decyl. In certain embodiments, alkyl groups are optionally substituted.

The term "C-i-6alkyl," as used herein, means a straight, branched chain, or cyclic (in this case, it would also be known as "cycloalkyi") hydrocarbon containing from 1 -6 carbon atoms.

The term "Ci-3alkyl," as used herein, means a straight or branched chain hydrocarbon containing from 1 -3 carbon atoms.

The term "alkenyl," as used herein, means a straight, branched chain, or cyclic (in which case, it would also be known as a "cycloalkenyl") hydrocarbon containing from 2-10 carbons and containing at least one carbon-carbon double bond formed by the removal of two hydrogens. In some embodiments, depending on the structure, an alkenyl group is a monoradical or a diradical {e.g., an alkenylene group). In some embodiments, alkenyl groups are optionally substituted. Examples of alkenyl include, but are not limited to, ethenyl, 2-propenyl, 2-methyl-2-propenyl, 3-butenyl, 4-pentenyl, 5-hexenyl, 2-heptenyl, and 2-methyl-1 -heptenyl. In certain embodiments, alkenyl groups are optionally substituted.

The term "C2-6 alkenyl," as used herein, means a straight, branched chain, or cyclic (in this case, it would also be known as "cycloalkyi") hydrocarbon containing from 2-6 carbon atoms and at least one carbon-carbon double bond formed by the removal of two hydrogens.

The term "alkoxy," as used herein, means an alkyl group, as defined herein, appended to the parent molecular moiety through an oxygen atom. Examples of alkoxy include, but are not limited to, methoxy, ethoxy, propoxy, 2-propoxy, butoxy, tert-butoxy, pentyloxy, and hexyloxy.

An "amino acid" (or AA) or amino acid residue include but are not limited to the 20 naturally occurring amino acids acids commonly designated by three letter symbols and also includes 4-hydroxyproline, hydroxyysine, demosine, isodemosine, 3-methylhistidine, norvalin, beta-alanine, gamma-aminobutyric acid, homocysteine, homoserine, ornithine and methionine sulfone. The amino acid residue of the present application also include the corresponding N-methyl amino acids, such as

-N(CH3)CH2C(0)0- -NHC(0)CH2CH2CH(NHCH3)C(0)0-, etc. The amino acids, dipeptides, tripeptides, oligomers and polypeptides designated as -(AA)r- of the present application may include the corresponding non-N-alkylated amino acids and

peptides (such as non-N-methylated amino acids in the peptides), as well as a mixture of the non-N-alkylated amino acids and the N-alkylated amino acids of the peptides.

An "antibody-drug conjugate" or "ADC" is an antibody that is conjugated to one or more cytotoxins, through one or more linkers. An antibody-drug conjugate (ADC) may be of the formula A-L-CTX, wherein A is an antibody, L is a linker, and CTX is a cytotoxin.

In the context of a polypeptide, the term "analog" as used herein refers to a

polypeptide that possesses a similar or identical function as a C10orf54 polypeptide, a fragment of a C10orf54 polypeptide, or an anti-C10orf54 antibody but does not necessarily comprise a similar or identical amino acid sequence of a C10orf54 polypeptide, a fragment of a C10orf54 polypeptide, or an anti-C10orf54 antibody, or possess a similar or identical structure of a C10orf54 polypeptide, a fragment of a C10orf54 polypeptide, or an anti-C10orf54 antibody. A polypeptide that has a similar amino acid sequence refers to a polypeptide that satisfies at least one of the following: (a) a polypeptide having an amino acid sequence that is at least 30%, at least 35%, at least 40%, at least 45%, at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or at least 99% identical to the amino acid sequence of a C10orf54 polypeptide (e.g., SEQ ID NO: 1079), a fragment of a C10orf54 polypeptide, or an anti-C10orf54 antibody described herein; (b) a polypeptide encoded by a nucleotide sequence that hybridizes under stringent conditions to a nucleotide sequence encoding a C10orf54 polypeptide, a fragment of a C10orf54 polypeptide, or an anti-C10orf54 antibody (or VH or VL region thereof) described herein of at least 5 amino acid residues, at least 10 amino acid residues, at least 15 amino acid residues, at least 20 amino acid residues, at least 25 amino acid residues, at least 40 amino acid residues, at least 50 amino acid residues, at least 60 amino residues, at least 70 amino acid residues, at least 80 amino acid residues, at least 90 amino acid residues, at least 100 amino acid residues, at least 125 amino acid residues, or at least 150 amino acid residues (see, e.g., Sambrook et al. (2001 ) Molecular Cloning: A

Laboratory Manual, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY; Maniatis et al. (1982) Molecular Cloning: A Laboratory Manual, Cold Spring Harbor Press, Cold Spring Harbor, NY); and (c) a polypeptide encoded by a nucleotide

sequence that is at least 30%, at least 35%, at least 40%, at least 45%, at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or at least 99% identical to the nucleotide sequence encoding a C10orf54 polypeptide, a fragment of a C10orf54 polypeptide, or an anti-C10orf54 antibody (or VH or VL region thereof) described herein. A

polypeptide with similar structure to a C10orf54 polypeptide, a fragment of a C10orf54 polypeptide, or an anti-C10orf54 antibody described herein refers to a polypeptide that has a similar secondary, tertiary or quaternary structure of a C10orf54

polypeptide, a fragment of a C10orf54, or a C10orf54 antibody described herein. The structure of a polypeptide can determined by methods known to those skilled in the art, including but not limited to, X-ray crystallography, nuclear magnetic resonance, and crystallographic electron microscopy.

As used herein, an "antagonist" or "inhibitor" of C10orf54 refers to a molecule that is capable of inhibiting or otherwise decreasing one or more of the biological activities of C10orf54, such as in a cell expressing C10orf54 or in a cell expressing a C10orf54 ligand, such as a C10orf54 receptor. In some embodiments, an antagonist of

C10orf54 {e.g., an antagonistic antibody provided herein) may, for example, act by inhibiting or otherwise decreasing the activation and/or cell signaling pathways of the cell expressing a C10orf54 or a C10orf54 receptor, thereby inhibiting a C10orf54-mediated biological activity of the cell the relative to the C10orf54-mediated biological activity in the absence of antagonist. In certain embodiments the antibodies provided herein are antagonistic anti-C10orf54 antibodies.

The terms "antibody" and "immunoglobulin" or "Ig" are used interchangeably herein, and are intended to include a polypeptide product of B cells within the

immunoglobulin class of polypeptides that is able to bind to a specific molecular antigen and is composed of two identical pairs of polypeptide chains, wherein each pair has one heavy chain (about 50-70 kDa) and one light chain (about 25 kDa) and each amino-terminal portion of each chain includes a variable region of about 100 to about 130 or more amino acids and each carboxy-terminal portion of each chain includes a constant region (See, Borrebaeck (ed.) (1995) Antibody Engineering, Second Ed. , Oxford University Press. ; Kuby (1997) Immunology, Third Ed. , W. H. Freeman and Company, New York). In specific embodiments, the specific molecular

antigen can be bound by an antibody provided herein includes the target C10orf54 polypeptide, fragment or epitope.

Antibodies also include, but are not limited to, synthetic antibodies, monoclonal antibodies, recombinantly produced antibodies, multispecific antibodies (including bi-specific antibodies), human antibodies, humanized antibodies, camelized antibodies, chimeric antibodies, intrabodies, anti-idiotypic (anti-Id) antibodies, and functional fragments of any of the above, which refers a portion of an antibody heavy or light chain polypeptide that retains some or all of the binding activity of the antibody from which the fragment was derived. Non-limiting examples of functional fragments include single-chain Fvs (scFv) {e.g., including monospecific, bispecific, etc.), Fab fragments, F(ab') fragments, F(ab)2 fragments, F(ab')2 fragments, disulfide-linked Fvs (sdFv), Fd fragments, Fv fragments, diabody, triabody, tetrabody and minibody. In particular, antibodies provided herein include immunoglobulin molecules and immunologically active portions of immunoglobulin molecules, e.g., antigen binding domains or molecules that contain an antigen-binding site that binds to a C10orf54 antigen {e.g., one or more complementarity determining regions (CDRs) of an anti-C10orf54 antibody). Such antibody fragments can be found described in, for example, Harlow and Lane, Antibodies: A Laboratory Manual, Cold Spring Harbor Laboratory, New York (1989); Myers (ed.), Molec. Biology and Biotechnology: A Comprehensive Desk Reference, New York: VCH Publisher, Inc. ; Huston et al. , Cell Biophysics, 22: 189-224 (1993); Pltickthun and Skerra, Meth. Enzymol. , 178:497-515 (1989) and in Day, E. D. , Advanced Immunochemistry, Second Ed. , Wiley-Liss, Inc. , New York, NY (1990). The antibodies provided herein can be of any type {e.g., IgG, IgE, IgM, IgD, IgA and IgY), any class {e.g., lgG1 , lgG2, lgG3, lgG4, lgA1 and lgA2), or any subclass {e.g., lgG2a and lgG2b) of immunoglobulin molecule. An anti-C10orf54 antibodies provided herein can be agonistic antibodies or antagonistic antibodies.

The terms "antibodies that specifically bind to C10orf54," "antibodies that specifically bind to a C10orf54 epitope," "anti-C10orf54 antibodies" and analogous terms are also used interchangeably herein and refer to antibodies that specifically bind to a

C10orf54 polypeptide, such as a C10orf54 antigen or epitope. Such antibodies include humanized antibodies. An antibody that specifically binds to a C10orf54 antigen may be cross-reactive with related antigens. In certain embodiments, an

antibody that specifically binds to a C10orf54 antigen does not cross-react with other antigens. An antibody that specifically binds to a C10orf54 antigen can be identified, for example, by immunoassays, BIAcore, or other techniques known to those of skill in the art. An antibody binds specifically to a C10orf54 antigen when it binds to a C10orf54 antigen with higher affinity than to any cross-reactive antigen as determined using experimental techniques, such as radioimmunoassays (RIA) and enzyme-linked immunosorbent assays (ELISAs). Typically a specific or selective reaction will be at least twice background signal or noise and more typically more than 10 times background. See, e.g., Paul, ed. , 1989, Fundamental Immunology Second Edition, Raven Press, New York at pages 332-336 for a discussion regarding antibody specificity. In certain embodiments, an antibody "which binds" an antigen of interest is one that binds the antigen with sufficient affinity such that the antibody is useful as a diagnostic and/or therapeutic agent in targeting a cell or tissue expressing the antigen, and does not significantly cross-react with other proteins. In such

embodiments, the extent of binding of the antibody to a "non-target" protein will be less than about 10% of the binding of the antibody to its particular target protein as determined by fluorescence activated cell sorting (FACS) analysis or

radioimmunoprecipitation (RIA). With regard to the binding of an antibody to a target molecule, the term "specific binding" or "specifically binds to" or is "specific for" a particular polypeptide or an epitope on a particular polypeptide target means binding that is measurably different from a non-specific interaction. Specific binding can be measured, for example, by determining binding of a molecule compared to binding of a control molecule, which generally is a molecule of similar structure that does not have binding activity. For example, specific binding can be determined by competition with a control molecule that is similar to the target, for example, an excess of non-labeled target. In this case, specific binding is indicated if the binding of the labeled target to a probe is competitively inhibited by excess unlabeled target. The term "specific binding" or "specifically binds to" or is "specific for" a particular polypeptide or an epitope on a particular polypeptide target as used herein can be exhibited, for example, by a molecule having a Kd for the target of at least about 10"4 M,

alternatively at least about 10"5 M, alternatively at least about 10"6 M, alternatively at least about 10"7 M, alternatively at least about 10"8 M, alternatively at least about 10"9 M, alternatively at least about 10"10 M, alternatively at least about 10"11 M,

alternatively at least about 10"12 M, or greater. In one embodiment, the term "specific

binding" refers to binding where a molecule binds to a particular polypeptide or epitope on a particular polypeptide without substantially binding to any other polypeptide or polypeptide epitope. In certain embodiments, an antibody that binds to C10orf54 has a dissociation constant (Kd) of < 1 μΜ, < 100 nM, < 10 nM, < 1 nM, or < 0.1 nM. In certain embodiments, anti- C10orf54 antibody binds to an epitope of C10orf54 that is conserved among C10orf54 from different species.

An "anti-c10orf54 antibody" or "an antibody that binds to C10orf54 " refers to an antibody that is capable of binding C10orf54, including, for example, an antibody, with sufficient affinity such that the antibody is useful as a diagnostic and/or therapeutic agent in targeting C10orf54. Such antibodies include humanized antibodies.

Preferably, the extent of binding of an anti-C10orf54 antibody to an unrelated, non-C10orf54 protein is less than about 10% of the binding of the antibody to C10orf54 as measured, e.g., by fluorescence activated cell sorting (FACS) analysis or a

radioimmunoassay (RIA). An antibody that '"specifically binds to" or is "specific for" C10orf54 is defined as above. In certain embodiments, an antibody that binds to C10orf54 has a dissociation constant (Kd) of < 1 μΜ, < 100 nM, < 10 nM, < 1 nM, or < 0.1 nM. In certain embodiments, anti-C10orf54 antibody binds to an epitope of C10orf54 that is conserved among C10orf54 from different species.

An "antigen" is a predetermined antigen to which an antibody can selectively bind. The target antigen may be a polypeptide, carbohydrate, nucleic acid, lipid, hapten or other naturally occurring or synthetic compound. In specific embodiments, the target antigen is a polypeptide.

The term "antigen binding fragment," "antigen binding domain," "antigen binding region," and similar terms refer to that portion of an antibody which comprises the amino acid residues that interact with an antigen and confer on the binding agent its specificity and affinity for the antigen {e.g., the complementarity determining regions (CDRs)).

The terms "binds" or "binding" as used herein refer to an interaction between molecules to form a complex. Interactions can be, for example, non-covalent interactions including hydrogen bonds, ionic bonds, hydrophobic interactions, and/or van der Waals interactions. A complex can also include the binding of two or more molecules held together by covalent or non-covalent bonds, interactions or forces. The strength of the total non-covalent interactions between a single antigen-binding site on an antibody and a single epitope of a target molecule, such as C10orf54, is the affinity of the antibody or functional fragment for that epitope. The ratio of association (ki) to dissociation (k.i) of an antibody to a monovalent antigen (kil k.i) is the association constant K, which is a measure of affinity. The value of K varies for different complexes of antibody and antigen and depends on both k-ι and k.-ι. The association constant for an antibody provided herein can be determined using any method provided herein or any other method well known to those skilled in the art. The affinity at one binding site does not always reflect the true strength of the interaction between an antibody and an antigen. When complex antigens containing multiple, repeating antigenic determinants, such as a polyvalent C10orf54, come in contact with antibodies containing multiple binding sites, the interaction of antibody with antigen at one site will increase the probability of a reaction at a second site. The strength of such multiple interactions between a multivalent antibody and antigen is called the avidity. The avidity of an antibody can be a better measure of its binding capacity than is the affinity of its individual binding sites. For example, high avidity can compensate for low affinity as is sometimes found for pentameric IgM antibodies, which can have a lower affinity than IgG, but the high avidity of IgM, resulting from its multivalence, enables it to bind antigen effectively.

The term "C10orf54" or "C10orf54 polypeptide" and similar terms refers to the polypeptide ("polypeptide," "peptide" and "protein" are used interchangeably herein) encoded by the human Chromosome 10 Open Reading Frame 54 (C10orf54) gene, which is also known in the art as B7-H5, platelet receptor Gi24, GI24, Stress Induced Secreted Proteinl , SISP1 , and PP2135, comprising the amino acid sequence of:

1 mgvptaleag swrwgsllfa lflaaslgpv aafkvatpys lyvcpegqnv tltcrllgpv

61 dkghdvtfyk twyrssrgev qtcserrpir nltfqdlhlh hgghqaants hdlaqrhgle

121 sasdhhgnfs itmrnltlld sglyccl ve irhhhsehrv hgamelqvqt gkdapsnc v

181 ypsssqdsen itaaalatga civgilclpl illlvykqrq aasnrraqel vrmdsniqgi 241 enpgfeaspp aqgipeakvr hplsyvaqrq psesgrhlls epstplsppg pgdvffpsld

301 pvpdspnfev I (SEQ ID NO: 1079)

and related polypeptides, including SNP variants thereof. The C10orf54 polypeptide has been shown to or is predicted to comprise several distinct regions within the

amino acid sequence including: a signal sequence (residues 1 -32; see Zhang et al., Protein Sci. 13:2819-2824 (2004)); an immunoglobulin domain - IgV-like (residues 33-162); and a transmembrane region (residues 195-215). The mature C10orf54 protein includes amino acid residues 33-31 1 of SEQ ID NO: 1079. The extracellular domain of the C10orf54 protein includes amino acid residues 33-194 of SEQ ID NO: 1079. Related polypeptides include allelic variants {e.g., SNP variants); splice variants; fragments; derivatives; substitution, deletion, and insertion variants; fusion

polypeptides (e.g. , chimeric proteins); and interspecies homologs, preferably, which retain C10orf54 activity and/or are sufficient to generate an anti-C10orf54 immune response. As those skilled in the art will appreciate, an anti-C10orf54 antibody provided herein can bind to a C10orf54 polypeptide, polypeptide fragment, antigen, and/or epitope, as an epitope is part of the larger antigen, which is part of the larger polypeptide fragment, which, in turn, is part of the larger polypeptide. C10orf54 can exist in a native or denatured form. The C10orf54 polypeptides described herein may be isolated from a variety of sources, such as from human tissue types or from another source, or prepared by recombinant or synthetic methods. A "native sequence C10orf54 polypeptide" comprises a polypeptide having the same amino acid sequence as the corresponding C10orf54 polypeptide derived from nature. Such native sequence C10orf54 polypeptides can be isolated from nature or can be produced by recombinant or synthetic means. The term "native sequence C10orf54 polypeptide" specifically encompasses naturally-occurring truncated or secreted forms of the specific C10orf54 polypeptide (e.g., an extracellular domain sequence), naturally-occurring variant forms (e.g., alternatively spliced forms) and naturally-occurring allelic variants of the polypeptide.

A cDNA nucleic acid sequence encoding the C10orf54 polypeptide comprises:

1 atgggcgtcc ccacggccct ggaggccggc agctggcgct ggggatccct gctcttcgct

61 ctcttcctgg ctgcgtccct aggtccggtg gcagccttca aggtcgccac gccgtattcc

121 ctgtatgtct gtcccgaggg gcagaacgtc accctcacct gcaggctctt gggccctgtg

181 gacaaagggc acgatgtgac cttctacaag acgtggtacc gcagctcgag gggcgaggtg 241 cagacctgct cagagcgccg gcccatccgc aacctcacgt tccaggacct tcacctgcac

301 catggaggcc accaggctgc caacaccagc cacgacctgg ctcagcgcca cgggctggag

361 tcggcctccg accaccatgg caacttctcc atcaccatgc gcaacctgac cctgctggat

421 agcggcctct actgctgcct ggtggtggag atcaggcacc accactcgga gcacagggtc

481 catggtgcca tggagctgca ggtgcagaca ggcaaagatg caccatccaa ctgtgtggtg 541 tacccatcct cctcccagga tagtgaaaac atcacggctg cagccctggc tacgggtgcc

601 tgcatcgtag gaatcctctg cctccccctc atcctgctcc tggtctacaa gcaaaggcag

661 gcagcctcca accgccgtgc ccaggagctg gtgcggatgg acagcaacat tcaagggatt

721 gaaaaccccg gctttgaagc ctcaccacct gcccagggga tacccgaggc caaagtcagg

781 caccccctgt cctatgtggc ccagcggcag ccttctgagt ctgggcggca tctgctttcg 841 gagcccagca cccccctgtc tcctccaggc cccggagacg tcttcttccc atccctggac 901 cctgtccctg actctccaaa ctttgaggtc atctag (SEQ ID NO: 1080)

Orthologs to the C10orf54 polypeptide are also well known in the art. For example, the mouse ortholog to the C10orf54 polypeptide is V-region |mmunoglobulin-containing Suppressor of T cell Activation (VISTA) (also known as PD-L3, PD-1 H, PD-XL, Pro1412 and UNQ730), which shares approximately 70% sequence identity to the human polypeptide. Orthologs of C10orf54 can also be found in additional organisms including chimpanzee, cow, rat and zebrafish.

A "C10orf54-expressing cell," "a cell having expression of C10orf54" or a grammatical equivalent thereof refers to a cell that expresses endogenous or transfected C10orf54 on the cell surface. C10orf54 expressing cells include a C10orf54-berring tumor cells, regulatory tumor cells (e.g. , CD4+ Foxp3+ regulatory T cells), myeloid-derived suppressor cells (e.g. , CD1 1 b+ or CD1 1 bhigh myeloid-derived suppressor cells) and/or suppressive dendritic cells (e.g. , CD1 1 b+ or CD1 1 bhigh dendritic cells). A cell expressing C10orf54 produces sufficient levels of C10orf54 on its surface, such that an anti-C10orf54 antibody can bind thereto. In some aspect, such binding may have a therapeutic effect with respect to the cancer. A cell that "overexpresses" C10orf54 is one that has significantly higher levels of C10orf54 at the cell surface thereof, compared to a cell of the same tissue type that is known to express C10orf54. Such overexpression may be caused by gene amplification or by increased transcription or translation. C10orf54 overexpression may be determined in a diagnostic or prognostic assay by evaluating increased levels of the C10orf54 protein present on the surface of a cell (e.g. via an immunohistochemistry assay; FACS analysis).

Alternatively, or additionally, one may measure levels of C10orf54-encoding nucleic acid or mRNA in the cell, e.g. via fluorescent in situ hybridization; (FISH; see

W098/45479 published October, 1998), Southern blotting, Northern blotting, or polymerase chain reaction (PCR) techniques, such as real time quantitative PCR (RT-PCR). Aside from the above assays, various in vivo assays are available to the skilled practitioner. For example, one may expose cells within the body of the patient to an antibody which is optionally labeled with a detectable agent, and binding of the antibody to cells in the patient can be evaluated, e.g. by external scanning for radioactivity or by analyzing a biopsy taken from a patient previously exposed to the antibody. A C10orf54-expressing tumor cell includes, but is not limited to, acute myeloid leukemia (AML) tumor cells.

A "C10orf54-mediated disease," "C10orf54-mediated disorder" and "C10orf54-mediated condition" are used interchangeably and refer to any disease, disorder or condition that is completely or partially caused by or is the result of C10orf54. Such diseases, disorders or conditions include those caused by or otherwise associated with C10orf54, including by or associated with C10orf54-expressing cells (e.g. , tumor cells, myeloid-derived suppressor cells (MDSC), suppressive dendritic cells

(suppressive DC), and /or regulatory T cells (T regs)). In certain embodiments, C10orf54 is aberrantly {e.g., highly) expressed on the surface of a cell. In some embodiments, C10orf54 may be aberrantly upregulated on a particular cell type. In other embodiments, normal, aberrant or excessive cell signaling is caused by binding of C10orf54 to a C10orf54 ligand, which can bind or otherwise interact with C10orf54.

The terms "cell proliferative disorder" and "proliferative disorder" refer to disorders that are associated with some degree of abnormal cell proliferation. In one

embodiment, the cell proliferative disorder is a tumor or cancer. "Tumor," as used herein, refers to all neoplastic cell growth and proliferation, whether malignant or benign, and all pre-cancerous and cancerous cells and tissues. The terms "cancer," "cancerous," "cell proliferative disorder," "proliferative disorder" and "tumor" are not mutually exclusive as referred to herein. The terms "cancer" and "cancerous" refer to or describe the physiological condition in mammals that is typically characterized by unregulated cell growth. Examples of cancer include, but are not limited to, carcinoma, lymphoma, blastoma, sarcoma, and leukemia or lymphoid malignancies. More particular examples of such cancers include squamous cell cancer (e.g.

epithelial squamous cell cancer), lung cancer including small-cell lung cancer, non-small cell lung cancer, adenocarcinoma of the lung and squamous carcinoma of the lung, cancer of the peritoneum, hepatocellular cancer, gastric or stomach cancer including gastrointestinal cancer, pancreatic cancer, glioblastoma, cervical cancer, ovarian cancer, oral cancer, liver cancer, bladder cancer, cancer of the urinary tract, hepatoma, breast cancer, colon cancer, rectal cancer, colorectal cancer, endometrial or uterine carcinoma, salivary gland carcinoma, kidney or renal cancer, prostate

cancer, vulval cancer, thyroid cancer, hepatic carcinoma, anal carcinoma, penile carcinoma, melanoma, multiple myeloma and B-cell lymphoma, brain cancer, skin cancer, esophagus cancer as well as head and neck cancer, and associated metastases.

The term "carrier" refers to a diluent, adjuvant {e.g., Freund's adjuvant (complete and incomplete)), excipient, or vehicle with which the therapeutic is administered. Such pharmaceutical carriers can be sterile liquids, such as water and oils, including those of petroleum, animal, vegetable or synthetic origin, such as peanut oil, soybean oil, mineral oil, sesame oil and the like. Water is a exemplary carrier when the

pharmaceutical composition is administered intravenously. Saline solutions and aqueous dextrose and glycerol solutions can also be employed as liquid carriers, particularly for injectable solutions. Suitable pharmaceutical excipients include starch, glucose, lactose, sucrose, gelatin, malt, rice, flour, chalk, silica gel, sodium stearate, glycerol monostearate, talc, sodium chloride, dried skim milk, glycerol, propylene, glycol, water, ethanol and the like. The composition, if desired, can also contain minor amounts of wetting or emulsifying agents, or pH buffering agents. These compositions can take the form of solutions, suspensions, emulsion, tablets, pills, capsules, powders, sustained-release formulations and the like. Oral formulation can include standard carriers such as pharmaceutical grades of mannitol, lactose, starch, magnesium stearate, sodium saccharine, cellulose, magnesium carbonate, etc.

Examples of suitable pharmaceutical carriers are described in Remington's

Pharmaceutical Sciences (1990) Mack Publishing Co., Easton, PA. Such

compositions will contain a prophylactically or therapeutically effective amount of the antibody, e.g., in isolated or purified form, together with a suitable amount of carrier so as to provide the form for proper administration to the patient. The formulation should suit the mode of administration.

The term "chemical group," as used herein, refers to two or more atoms bound together as a single unit and forming part of a molecule.

A "chemotherapeutic agent" is a chemical agent {e.g., compound or drug) useful in the treatment of cancer, regardless of mechanism of action. Chemotherapeutic agents include compounds used in targeted therapy and conventional chemotherapy. Examples of chemotherapeutic agents include, but are not limited to, alkylating

agents such as thiotepa and CYTOXAN® cyclosphosphamide; alkyl sulfonates such as busulfan, improsulfan and piposulfan; aziridines such as benzodopa, carboquone, meturedopa, and uredopa; ethylenimines and methylamelamines including

altretamine, triethylenemelamine, trietylenephosphoramide,

triethiylenethiophosphoramide and trimethylolomelamine; acetogenins (especially bullatacin and bullatacinone); delta-9-tetrahydrocannabinol (dronabinol, AR1 NOL®); beta-lapachone; lapachol; colchicines; betulinic acid; a camptothecin (including the synthetic analogue topotecan (HYCAMTIN®), CPT-1 1 (irinotecan, CAMPTOSAR®), acetylcamptothecin, scopolectin, and 9-aminocamptothecin); bryostatin; callystatin; CC-1065 (including its adozelesin, carzelesin and bizelesin synthetic analogues); podophyllotoxin; podophyllinic acid; teniposide; cryptophycins (particularly

cryptophycin 1 and cryptophycin 8); dolastatin; duocarmycin (including the synthetic analogues, KW-2189 and CB1 -TM1 ); eleutherobin; pancratistatin; a sarcodictyin; spongistatin; nitrogen mustards such as chlorambucil, chlornaphazine,

cholophosphamide, estramustine, ifosfamide, mechlorethamine, mechlorethamine oxide hydrochloride, melphalan, novembichin, phenesterine, prednimustine, trofosfamide, uracil mustard; nitrosureas such as carmustine, chlorozotocin, fotemustine, lomustine, nimustine, and ranimnustine; antibiotics such as the enediyne antibiotics {e.g., calicheamicin, especially calicheamicin gammal I and calicheamicin omega II (see, e.g., Agnew, Chem Intl. Ed. Engl. 33: 183-186 (1994)); dynemicin, including dynemicin A; an esperamicin; as well as neocarzinostatin chromophore and related chromoprotein enediyne antiobiotic chromophores), aclacinomysins, actinomycin, authramycin, azaserine, bleomycins, cactinomycin, carabicin, caminomycin, carzinophilin, chromomycinis, dactinomycin, daunorubicin, detorubicin, 6-diazo-5-oxo-L-norleucine, ADRIAMYCIN®, doxorubicin (including morpholino-doxorubicin, cyanomorpholino-doxorubicin, 2-pyrrolino-doxorubicin and

deoxydoxorubicin), epirubicin, esorubicin, idarubicin, marcellomycin, mitomycins such as mitomycin C, mycophenolic acid, nogalamycin, olivomycins, peplomycin, potfiromycin, puromycin, quelamycin, rodorubicin, streptonigrin, streptozocin, tubercidin, ubenimex, zinostatin, zorubicin; anti-metabolites such as methotrexate and 5-fluorouracil (5-FU); folic acid analogues such as denopterin, methotrexate, pteropterin, trimetrexate; purine analogs such as fludarabine, 6-mercaptopurine, thiamiprine, thioguanine; pyrimidine analogs such as ancitabine, azacitidine, 6-azauridine, carmofur, cytarabine, dideoxyuridine, doxifluridine, enocitabine,

floxuridine; androgens such as calusterone, dromostanolone propionate, epitiostanol, mepitiostane, testolactone; anti-adrenals such as aminoglutethimide, mitotane, trilostane; folic acid replenisher such as frolinic acid; aceglatone; aldophosphamide glycoside; aminolevulinic acid; eniluracil; amsacrine; bestrabucil; bisantrene;

edatraxate; defofamine; demecolcine; diaziquone; elfornithine; elliptinium acetate; an epothilone; etoglucid; gallium nitrate; hydroxyurea; lentinan; lonidainine;

maytansinoids such as maytansine and ansamitocins; mitoguazone; mitoxantrone; mopidanmol; nitraerine; pentostatin; phenamet; pirarubicin; losoxantrone; 2-ethylhydrazide; procarbazine; PSK® polysaccharide complex (JHS Natural Products, Eugene, Oreg.); razoxane; rhizoxin; sizofuran; spirogermanium; tenuazonic acid; triaziquone; 2,2',2"-trichlorotriethylamine; trichothecenes (especially T-2 toxin, verracurin A, roridin A and anguidine); urethan; vindesine (ELDISINE®, FILDESIN®); dacarbazine; mannomustine; mitobronitol; mitolactol; pipobroman; gacytosine;

arabinoside ("Ara-C"); thiotepa; taxoids, e.g., TAXOL® paclitaxel (Bristol-Myers Squibb Oncology, Princeton, N.J.), ABRAXANE™ Cremophor-free, albumin-engineered nanoparticle formulation of paclitaxel (American Pharmaceutical Partners, Schaumberg, IL), and TAXOTERE® doxetaxel (Rhone-Poulenc Rorer, Antony, France); chloranbucil; gemcitabine (GEMZAR®); 6-thioguanine; mercaptopurine; methotrexate; platinum analogs such as cisplatin and carboplatin; vinblastine

(VELBAN®); platinum; etoposide (VP- 16); ifosfamide; mitoxantrone; vincristine (ONCOVIN®); oxaliplatin; leucovovin; vinorelbine (NAVELBINE®); novantrone;

edatrexate; daunomycin; aminopterin; ibandronate; topoisomerase inhibitor RFS 2000; difluoromethylornithine (DMFO); retinoids such as retinoic acid; capecitabine (XELODA®); pharmaceutically acceptable salts, acids or derivatives of any of the above; as well as combinations of two or more of the above such as CHOP, an abbreviation for a combined therapy of cyclophosphamide, doxorubicin, vincristine, and prednisolone, and FOLFOX, an abbreviation for a treatment regimen with oxaliplatin (ELOXATIN™) combined with 5-FU and leucovovin. Additional

chemotherapeutic agents include cytotoxic agents useful as antibody drug

conjugates, such as maytansinoids (DM1 and DM4, for example) and auristatins (MMAE and MMAF, for example).

WHAT IS CLAIMED:

An isolated antibody that binds to a first group of C10orf54 proteins or chimeric proteins designated CC1 (SEQ ID NO: 1079), CC4 (SEQ ID NO: 1245), CC5 (SEQ ID NO: 1246), CC8 (SEQ ID NO: 1249), and CC10 (SEQ ID NO: 1251 ), and does not bind to a second groupd of C10orf54 proteins or chimeric proteins designated CC2 (SEQ ID NO: 1243), CC3 (SEQ ID NO: 1244), CC6 (SEQ ID NO: 1247), CC7 (SEQ ID NO: 1248), and CC9 (SEQ ID NO: 1250).

The isolated antibody of claim 1 , wherein the antibody comprises:

(a) a heavy chain variable (VH) region comprising:

(1 ) a VH CDR1 having an amino acid sequence selected from the group consisting of SEQ ID NOS: 30, 1099, 1 104, 1 105, 1 1 10, 1291 -1305, 131 1 -1315, and 1321 -1325;

(2) a VH CDR2 having an amino acid sequence selected from the group consisting of SEQ ID NOS: 37, 849, 1082, 1088, 1093, 1098, 1336- 1344, 1348-1367, 1373, 1374, and 1556-1559; and

(3) a VH CDR3 having an amino acid sequence selected from the group consisting of SEQ ID NOS: 38, 1083, 1089, 1094, 1385-1404, and 1409-1412;

and/or

(b) a light chain variable (VL) region comprising:

(1 ) a VL CDR1 having an amino acid sequence selected from the group consisting of SEQ ID NOS: 45, 1 102, 1 108, 1 1 13, 1425-1430, 1432- 1457, 1681 -1684, and 1915;

(2) a VL CDR2 having an amino acid sequence selected from the group consisting of SEQ ID NOS: 40, 157, 1 103, 1 1 14, 1473-1481 , 1526- 1528, 1630-1633, and 1685-1688; and

(3) a VL CDR3 having an amino acid sequence selected from the group consisting of SEQ ID NOS: 1493-1507, 151 1 -1516, and 1523-1525.

The antibody of claim 1 , wherein the antibody is humanized.

4. The antibody of claim 2 or 3, wherein the VH region further comprises: (1 ) a VH FR1 having an amino acid sequence selected from the group consisting of SEQ ID NOS: 51 , 1550-1555, 105, and 1649-1652;

(2) a VH FR2 having an amino acid sequence selected from the group consisting of SEQ ID NOS: 52 and 106;

(3) a VH FR3 having an amino acid sequence selected from the group consisting of SEQ ID NOS: 1560-1614, and 1653-1679; and/or

(4) a VH FR4 having an amino acid sequence selected from the group consisting of SEQ ID NOS: 54 and 1680.

5. The antibody of claim 2 or 3, wherein the VL region further comprises:

(1 ) a VL FR1 having an amino acid sequence selected from the group consisting of SEQ ID NOS: 1615-1629, 79, and 278;

(2) a VL FR2 having an amino acid sequence selected from the group consisting of SEQ ID NOS: 92, 80, and 284;

(3) a VL FR3 having an amino acid sequence selected from the group consisting of SEQ ID NOS: 1634-1648, 81 , 1689-1714, 285, 286, and 288; and/or

(4) a VL FR4 having an amino acid of SEQ ID NO: 78.

6. The antibody of claim 2 or 3, wherein the antibody comprises a VH region and a VL region, wherein the VH region further comprises:

(1 ) a VH FR1 having an amino acid sequence selected from the group consisting of SEQ ID NOS: 51 , 1550-1555, 105, and 1649-1652;

(2) a VH FR2 having an amino acid sequence selected from the group consisting of SEQ ID NOS: 52 and 106;

(3) a VH FR3 having an amino acid sequence selected from the group consisting of SEQ ID NOS: 1560-1614, and 1653-1679; and/or

(4) a VH FR4 having an amino acid sequence selected from the group consisting of SEQ ID NOS: 54 and 1680; and

wherein the VL region further comprises:

a VL FR1 having an amino acid sequence selected from the group consisting of SEQ ID NOS: 1615-1629, 79, and 278;

(2) a VL FR2 having an amino acid sequence selected from the group consisting of SEQ ID NOS: 92, 80, and 284;

(3) a V|_ FR3 having an amino acid sequence selected from the group

consisting of SEQ ID NOS: 1634-1648, 81 , 1689-1714, 285, 286, and 288; and/or

(4) a VL FR4 having an amino acid sequence of SEQ ID NO: 78.

7. The antibody of any one of claims 1 to 6, wherein the antibody comprises:

(a) a VH region comprising:

(1 ) a VH CDR1 having an amino acid sequence of SEQ ID NO: 1296,

1297, 1298, 1299, or 1300;

(2) a VH CDR2 having an amino acid sequence of SEQ ID NO: 1354,

1355, 1356, 1357, 1358, 1556, 1557, 1558, or 1559; and

(3) a VH CDR3 having an amino acid sequence of SEQ ID NO: 1393,

1394, 1395, or 1396;

(b) a VL region comprising:

(1 ) a VL CDR1 having an amino acid sequence of SEQ ID NO: 1435, 1432, 1433, or 1436;

(2) a VL CDR2 having an amino acid sequence of SEQ ID NO: 1476, 1477, 1478, 1630, 1631 , 1632, or 1633; and

(3) a VL CDR3 having an amino acid sequence of SEQ ID NO: 1499, 1500, or 1501 .

8. The antibody of any one of claims 1 to 6, wherein the antibody comprises:

(a) a VH region comprising:

(1 ) a VH CDR1 having an amino acid sequence of SEQ ID NO: 1291 ,

1292, 1293, 1294, or 1295;

(2) a VH CDR2 having an amino acid sequence of SEQ ID NO: 1336,

1337, 1338, 1339, or 1340; and

(3) a VH CDR3 having an amino acid sequence of SEQ ID NO: 1385,

1386, 1387, or 1388;

and

(b) a VL region comprising:

(1 ) a VL CDR1 having an amino acid sequence of SEQ ID NO: 1425, 1426, 1427, or 1428;

(2) a VL CDR2 having an amino acid sequence of SEQ ID NO: 1473, 1474, or 1475; and

(3) a VL CDR3 having an amino acid sequence of SEQ ID NO: 1493, 1494, or 1495.

9. The antibody of any one of claims 1 to 6, wherein the antibody comprises:

(a) a VH region comprising:

(1 ) a VH CDR1 having an amino acid sequence of SEQ ID NO: 1291 ,

1292, 1293, 1294, or 1295;

(2) a VH CDR2 having an amino acid sequence of SEQ ID NO: 1341 ,

1342, 1338, 1343, or 1344; and

(3) a VH CDR3 having an amino acid sequence of SEQ ID NO: 1389,

1390, 1391 , or 1392;

and

(b) a VL region comprising:

(1 ) a VL CDR1 having an amino acid sequence of SEQ ID NO: 1425, 1426, 1427, or 1428;

(2) a VL CDR2 having an amino acid sequence of SEQ ID NO: 1473, 1474, or 1475; and

(3) a VL CDR3 having an amino acid sequence of SEQ ID NO: 1496, 1497, or 1498.

10. The antibody of any one of claims 1 to 6, wherein the antibody comprises:

(a) a VH region comprising:

(1 ) a VH CDR1 having an amino acid sequence of SEQ ID NO: 1291 ,

1292, 1293, 1294, or 1295;

(2) a VH CDR2 having an amino acid sequence of SEQ ID NO: 1348, 1337, 1338, 1349, or 1350; and

(3) a VH CDR3 having an amino acid sequence of SEQ ID NO: 1385,

1386, 1387, or 1388;

and

(b) a VL region comprising:

(1 ) a VL CDR1 having an amino acid sequence of SEQ ID NO: 1429, 1426, 1427, 1430, 1681 , 1682, 1683, or 1684;

(2) a VL CDR2 having an amino acid sequence of SEQ ID NO: 1473, 1474, 1475, 1685, 1686, 1687, or 1688; and

(3) a VL CDR3 having an amino acid sequence of SEQ ID NO: 1493, 1494, or 1495.

1 1 . The antibody of any one of claims 1 to 6, wherein the antibody comprises:

(a) a VH region comprising:

(1 ) a VH CDR1 having an amino acid sequence of SEQ ID NO: 1291 ,

1292, 1293, 1294, or 1295;

(2) a VH CDR2 having an amino acid sequence of SEQ ID NO: 1348,

1337, 1338, 1349, or 1350; and

(3) a VH CDR3 having an amino acid sequence of SEQ ID NO: 1385,

1386, 1387, or 1388;

and

(b) a VL region comprising:

(1 ) a VL CDR1 having an amino acid sequence of SEQ ID NO: 1429, 1426, 1427, or 1430;

(2) a VL CDR2 having an amino acid sequence of SEQ ID NO: 1473, 1474, or 1475; and

(3) a VL CDR3 having an amino acid sequence of SEQ ID NO: 1493, 1494, or 1495.

12. The antibody of any one of claims 1 to 6, wherein the antibody comprises: (a) a VH region comprising:

(1 ) a VH CDR1 having an amino acid sequence of SEQ ID NO: 1291 ,

1292, 1293, 1294, or 1295;

(2) a VH CDR2 having an amino acid sequence of SEQ ID NO: 1351 ,

1337, 1338, 1352, or 1353; and

(3) a VH CDR3 having an amino acid sequence of SEQ ID NO: 1385,

1386, 1387, or 1388;

and

(b) a VL region comprising:

(1 ) a VL CDR1 having an amino acid sequence of SEQ ID NO: 1425, 1426, 1427, or 1428;

(2) a VL CDR2 having an amino acid sequence of SEQ ID NO: 1473, 1474, or 1475; and

(3) a VL CDR3 having an amino acid sequence of SEQ ID NO: 1493, 1494, or 1495.

13. The antibody of any one of claims 1 to 6, wherein the antibody comprises:

(a) a VH region comprising:

(1 ) a VH CDR1 having an amino acid sequence of SEQ ID NO: 30, 1099, 1 104, 1 105, or 1 1 10;

(2) a VH CDR2 having an amino acid sequence of SEQ ID NO: 1359,

1360, 1361 , 1362, or 1363; and

(3) a VH CDR3 having an amino acid sequence of SEQ ID NO: 1397,

1398, 1399, or 1400;

and

(b) a VL region comprising:

(1 ) a VL CDR1 having an amino acid sequence of SEQ ID NO: 1437, 1451 , 1438, 1452, 1451 1439, 1453, 1450, or 1915;

(2) a VL CDR2 having an amino acid sequence of SEQ ID NO: 1526, 1479, 1527, 1480, 157, 1528, or 1481 ; and

(3) a VL CDR3 having an amino acid sequence of SEQ ID NO: 1523, 1502, 1524, 1503, 1525, or 1504.

The antibody of any one of claims 1 to 6, wherein the antibody comprises:

(a) a VH region comprising:

(1 ) a VH CDR1 having an amino acid sequence of SEQ ID NO: 1301 ,

1302, 1303, 1304, or 1305;

(2) a VH CDR2 having an amino acid sequence of SEQ ID NO: 1364,

1365, 1361 , 1366, or 1367; and

(3) a VH CDR3 having an amino acid sequence of SEQ ID NO: 1401 ,

1402, 1403, or 1404;

and

(b) a VL region comprising:

(1 ) a VL CDR1 having an amino acid sequence of SEQ ID NO: 1454, 1455, 1456, or 1457;

(2) a VL CDR2 having an amino acid sequence of SEQ ID NO: 40, 1 103, or 1 1 14; and

(3) a VL CDR3 having an amino acid sequence of SEQ ID NO: 1505, 1506, or 1507.

The antibody of any one of claims 1 to 6, wherein the antibody comprises:

(a) a VH region comprising:

(1 ) a VH CDR1 having an amino acid sequence of SEQ ID NO: 131 1 ,

1312, 1313, 1314, or 1315;

(2) a VH CDR2 having an amino acid sequence of SEQ ID NO: 37, 1082, 1088, 1093, or 1098; and

(3) a VH CDR3 having an amino acid sequence of SEQ ID NO: 1409,

1410, 141 1 , or 1412;

and

(b) a VL region comprising:

(1 ) a VL CDR1 having an amino acid sequence of SEQ ID NO: 45, 1 102, 1 108, or 1 1 13;

(2) a V|_ CDR2 having an amino acid sequence of SEQ ID NO: 40, 1 103, or 1 1 14; and

(3) a VL CDR3 having an amino acid sequence of SEQ ID NO: 151 1 , 1512, or 1513.

6. The antibody of any one of claims 1 to 6, wherein the antibody comprises:

(a) a VH region comprising:

(1 ) a VH CDR1 having an amino acid sequence of SEQ ID NO: 1321 ,

1322, 1323, 1324, or 1325;

(2) a VH CDR2 having an amino acid sequence of SEQ ID NO: 849, 1082,

1088, 1373, or 1374; and

(3) a VH CDR3 having an amino acid sequence of SEQ ID NO: 38, 1083,

1089, or 1094;

and

(b) a VL region comprising:

(1 ) a VL CDR1 having an amino acid sequence of SEQ ID NO: 45, 1 102, 1 108, or 1 1 13;

(2) a VL CDR2 having an amino acid sequence of SEQ ID NO: 40, 1 103, or 1 1 14; and

(3) a VL CDR3 having an amino acid sequence of SEQ ID NO: 1514, 1515, or 1516.

7. An isolated antibody that binds a first group of C10orf54 proteins or chimeric proteins designated CC1 (SEQ ID NO: 1079), CC4 (SEQ ID NO: 1245), CC5 (SEQ ID NO: 1246), and CC8 (SEQ ID NO: 1249), and does not bind to a second groupd of C10orf54 proteins or chimeric proteins designated CC2 (SEQ ID NO: 1243), CC3 (SEQ ID NO: 1244), CC6 (SEQ ID NO: 1247), CC7 (SEQ ID NO: 1248), CC9 (SEQ ID NO: 1250), and CC10 (SEQ ID NO: 1251 ), with the proviso that the isolated antibody does not comprise one or more CDR sequences selected from the group consisting of 30, 1099, 1 104, 1 105, 1110, 31, 1100, 1106, 1111, 1116, 32, 1101, 1107, 1112, 45, 1102, 1108, 1113, 40, 1103, 1114, 41, 1109, and 1115.

18. The isolated antibody of claim 17, wherein the antibody comprises:

(a) a heavy chain variable (VH) region comprising:

(1) a VH CDR1 having an amino acid sequence selected from the group consisting of SEQ ID NOS: 30, 1099, 1110, 1104, 1105, 1296-1300, 1306-1310, 1316-1320, and 1717-1720;

(2) a VH CDR2 having an amino acid sequence selected from the group consisting of SEQ ID NOS: 31, 37, 1082, 1088, 1092, 1098, 1100, 1106, 1111, 1116, 1354-1358, 1368-1372, 1829-1847, and 1917; and

(3) a VH CDR3 having an amino acid sequence selected from the group consisting of SEQ ID NOS: 32, 38, 1083, 1089, 1094, 1101 , 1107, 1112, 1393-1396, 1405-1408, 1413, 1414;

and/or

(b) a light chain variable (VL) region comprising:

(1) a VL CDR1 having an amino acid sequence selected from the group consisting of SEQ ID NOS: 45, 253-271 , 1102, 1108, 1113, 1431 -1434, 1458-1465, 1744-1822, 1878-1896;

(2) a VL CDR2 having an amino acid sequence selected from the group consisting of SEQ ID NOS: 40, 843-846, 1103, 1114, 1476-1478, 1482- 1487, 1898-1900; and

(3) a VL CDR3 having an amino acid sequence selected from the group consisting of SEQ ID NOS: 41 , 1109, 1115, 1499-1501 , 1508-1513.

19. The antibody of claim 17, wherein the antibody is humanized.

20. The antibody of claim 18 or 19, wherein the VH region further comprises:

(1) a VH FR1 having an amino acid sequence selected from the group

consisting of SEQ ID NOS: 51, 39, 1715, 1716, 1550, 1827, 1828, 105, 55, and 115-121;

(2) a VH FR2 having an amino acid sequence selected from the group

consisting of SEQ ID NOS: 52, 106, 63, 64, 56, 323-326, and 122-124; (3) a VH FR3 having an amino acid sequence selected from the group consisting of SEQ ID NOS: 1560, 1561 , 1721 -1742, 1566, 1567, 1571 , 1575, 1585, 1562, 1563, 1848-1875, 1565-1568, 1570-1572, 1574, 1575, 1577, 1578, 1581 , 1582, 1584, 1585, 1587, 1591 , 1593, 1594, 1597, 1602, 1603, 53, 107, 96-98, 292-318, 57, and 327-833; and/or

(4) a VH FR4 having an amino acid sequence selected from the group

consisting of SEQ ID NOS: 54 and 320.

21 . The antibody of claim 18 or 19, wherein the VL region further comprises:

(1 ) a VL FR1 having an amino acid sequence selected from the group

consisting of SEQ ID NOS: 1743, 75, 252, 1878, 1877, 79, and 277- 283;

(2) a VL FR2 having an amino acid sequence selected from the group

consisting of SEQ ID NOS: 1823-1826, 76, 80, and 284;

(3) a VL FR3 having an amino acid sequence selected from the group

consisting of SEQ ID NOS: 77, 276, 1901 , 81 , and 285-291 ; and/or

(4) a VL FR4 having an amino acid sequence of SEQ ID NO: 78.

22. The antibody of claim 18 or 19, wherein the antibody comprises a VH region and a VL region, wherein the VH region further comprises:

(1 ) a VH FR1 having an amino acid sequence selected from the group

consisting of SEQ ID NOS: 51 , 39, 1715, 1716, 1550, 1827, 1828, 105, 55, and 1 15-121 ;

(2) a VH FR2 having an amino acid sequence selected from the group

consisting of SEQ ID NOS: 52, 106, 63, 64, 56, 323-326, and 122-124;

(3) a VH FR3 having an amino acid sequence selected from the group

consisting of SEQ ID NOS: 1560, 1561 , 1721 -1742, 1566, 1567, 1571 , 1575, 1585, 1562, 1563, 1848-1875, 1565-1568, 1570-1572, 1574, 1575, 1577, 1578, 1581 , 1582, 1584, 1585, 1587, 1591 , 1593, 1594, 1597, 1602, 1603, 53, 107, 96-98, 292-318, 57, and 327-833; and/or

(4) a VH FR4 having an amino acid sequence selected from the group

consisting of SEQ ID NOS: 54 and 320; and

wherein the VL region further comprises:

(1 ) a VL FR1 having an amino acid sequence selected from the group consisting of SEQ ID NOS: 1743, 75, 252, 1878, 1877, 79, and 277- 283;

(2) a VL FR2 having an amino acid sequence selected from the group

consisting of SEQ ID NOS: 1823-1826, 76, 80, and 284;

(3) a VL FR3 having an amino acid sequence selected from the group

consisting of SEQ ID NOS: 77, 276, 1901 , 81 , and 285-291 ; and/or

(4) a VL FR4 having an amino acid sequence of SEQ ID NO: 78.

23. The antibody of any one of claims 17 to 22, wherein the antibody comprises:

(a) a VH region comprising:

(1 ) a VH CDR1 having an amino acid sequence of SEQ ID NO: 1296,

1297, 1298, 1299, or 1300;

(2) a VH CDR2 having an amino acid sequence of SEQ ID NO: 1354,

1355, 1356, 1357, or 1358; and

(3) a VH CDR3 having an amino acid sequence of SEQ ID NO: 1393,

1394, 1395, or 1396;

and

(b) a VL region comprising:

(1 ) a VL CDR1 having an amino acid sequence of SEQ ID NO: 1431 , 1432, 1433, or 1434;

(2) a VL CDR2 having an amino acid sequence of SEQ ID NO: 1476, 1477, or 1478; and

(3) a VL CDR3 having an amino acid sequence of SEQ ID NO: 1499, 1500, or 1501 .

24. The antibody of any one of claims 17 to 22, wherein the antibody comprises:

(a) a VH region comprising:

(1 ) a VH CDR1 having an amino acid sequence of SEQ ID NO: 1306,

1307, 1308, 1309, or 1310;

(2) a VH CDR2 having an amino acid sequence of SEQ ID NO: 1368,

1369, 1370, 1371 , or 1372; and

(3) a VH CDR3 having an amino acid sequence of SEQ ID NO: 1405, 1406, 1407, or 1408;

and

(b) a VL region comprising:

(1 ) a VL CDR1 having an amino acid sequence of SEQ ID NO: 1458, 1459, 1460, or 1461 ;

(2) a VL CDR2 having an amino acid sequence of SEQ ID NO: 1482, 1483, or 1484; and

(3) a VL CDR3 having an amino acid sequence of SEQ ID NO: 1508, 1509, or 1510.

25. The antibody of any one of claims 17 to 22, wherein the antibody comprises:

(a) a VH region comprising:

(1 ) a VH CDR1 having an amino acid sequence of SEQ ID NO: 1306,

1307, 1308, 1309, or 1310;

(2) a VH CDR2 having an amino acid sequence of SEQ ID NO: 1368,

1369, 1370, 1371 , 1372, 1829, 1830, 1831 , 1832, 1833, 1834, 1835, 1836, 1837, 1838, 1839, 1840, 1841 , 1842, 1843, 1844, 1845, 1846, or 1847; and

(3) a VH CDR3 having an amino acid sequence of SEQ ID NO: 1405,

1406, 1407, or 1408;

and

(b) a VL region comprising:

(1 ) a VL CDR1 having an amino acid sequence of SEQ ID NO: 1458, 1459, 1460, 1461 , 1878, 1879, 1880, 1881 , 1882, 1883, 1884, 1885, 1886, 1887, 1888, 1889, 1890, 1891 , 1892, 1893, 1894, 1895, or 1896;

(2) a VL CDR2 having an amino acid sequence of SEQ ID NO: 1485, 1486, 1487, 1897, 1898, 1899, or 1900; and

(3) a VL CDR3 having an amino acid sequence of SEQ ID NO: 1508, 1509, or 1510.

26. The antibody of any one of claims 17 to 22, wherein the antibody comprises:

(a) a VH region comprising:

(1 ) a VH CDR1 having an amino acid sequence of SEQ ID NO: 1316,

1317, 1318, 1319, or 1320;

(2) a VH CDR2 having an amino acid sequence of SEQ ID NO: 37, 1082,

1088, 1092, or 1098; and

(3) a VH CDR3 having an amino acid sequence of SEQ ID NO: 38, 1083,

1089, or 1094;

and

(b) a VL region comprising:

(1 ) a VL CDR1 having an amino acid sequence of SEQ ID NO: 1462, 1463, 1464, or 1465;

(2) a VL CDR2 having an amino acid sequence of SEQ ID NO: 40, 1 103, or 1 1 14; and

(3) a VL CDR3 having an amino acid sequence of SEQ ID NO: 151 1 , 1512, or 1513.

27. The antibody of any one of claims 17 to 22, wherein the antibody comprises:

(a) a VH region comprising:

(1 ) a VH CDR1 having an amino acid sequence of SEQ ID NO: 1316,

1317, 1318, 1319, 1320, 1717, 1718, 1719, or 1720;

(2) a VH CDR2 having an amino acid sequence of SEQ ID NO: 37, 1082, 1088, 1917, or 1098; and

(3) a VH CDR3 having an amino acid sequence of SEQ ID NO: 1413,

1414, 1089, or 1094;

and

(b) a VL region comprising:

(1 ) a VL CDR1 having an amino acid sequence of SEQ ID NO: 1462, 1463, 1464, 1465, 1744, 45, 1745, 1746, 1747, 1748, 1749, 1750, 1751 , 1752, 1753, 1754, 1755, 1756, 1757, 1758, 1759, 1760, 253, 254, 255, 256, 257, 258, 259, 1761 , 1762, 1763, 1764, 1765, 1766, 1767, 1768, 1769, 1770, 1771 , 1772, 1773, 1774, 1775, 1776, 1777, 1778, 1779, 1780, 1781 , 1782, 1783, 1784, 1785, 1786, 1787, 260, 1788, 1789, 1790, 1791 , 264, 268, 1792, 1793, 1794, 1795, 1796, 261 , 1797, 1798, 1799, 1800, 265, 269, 1801 , 1802, 1803, 1804, 1805, 262, 1806, 1807, 1808, 1809, 266, 270, 1810, 181 1 , 1812, 1813, 1814, 263, 1815, 1816, 1817, 1818, 267, 271 , 1819, 1820, 1821 , or 1822;

(2) a VL CDR2 having an amino acid sequence of SEQ ID NO: 40, 1 103, 1 1 14, 843, 844, 846, or 845; and

(3) a VL CDR3 having an amino acid sequence of SEQ ID NO: 151 1 , 1512, or 1513.

28. An isolated antibody that binds to a first group of C10orf54 proteins or

chimeric proteins designated CC1 (SEQ ID NO: 1079), CC4 (SEQ ID NO: 1245), and CC5 (SEQ ID NO: 1246), and does not bind to a second groupd of C10orf54 proteins or chimeric proteins designated (SEQ ID NO: 1243), CC3 (SEQ ID NO: 1244), CC6 (SEQ ID NO: 1247), CC7 (SEQ ID NO: 1248), CC8 (SEQ ID NO: 1249), CC9 (SEQ ID NO: 1250), and CC10 (SEQ ID NO: 1251 ), with the proviso that the isolated antibody does not comprise one or more CDR sequences selected from the group consisting of 36, 1081 , 1086, 1087, 1092, 37, 1082, 1088, 1093, 1098, 38, 1083, 1089, 1094, 45, 1084, 1090, 1095, 46, 1085, 1096, 47, 1091 , and 1097.

29. An isolated antibody that binds to a first group of C10orf54 proteins or

chimeric proteins designated CC1 (SEQ ID NO: 1079), CC4 (SEQ ID NO: 1245), CC5 (SEQ ID NO: 1246), CC8 (SEQ ID NO: 1249), and CC9 (SEQ ID NO: 1250), and does not bind to a second groupd of C10orf54 proteins or chimeric proteins designated CC2 (SEQ ID NO: 1243), CC3 (SEQ ID NO: 1244), CC6 (SEQ ID NO: 1247), CC7 (SEQ ID NO: 1248), CC9 (SEQ ID NO: 1250), and CC10 (SEQ ID NO: 1251 ), with the proviso that the isolated antibody does not comprise one or more CDR sequences selected from the group consisting of 33, 1 1 17, 1 122, 1 123, 1 128, 34, 1 1 18, 1 124, 1 129, 1 134, 35, 1 1 19, 1 125, 1 130, 42, 1 120, 1 126, 1 131 , 43, 1 121 , 1 132, 44, 1 127, and 1 133.

30. The antibody of claim 29, wherein the antibody comprises:

(a) a heavy chain variable (VH) region comprising:

(1 ) a VH CDR1 having an amino acid sequence selected from the group consisting of SEQ ID NOS: 33, 1 1 17, 1 122, 1 123, and 1 128;

(2) a VH CDR2 having an amino acid sequence selected from the group consisting of SEQ ID NOS: 34, 1082, 1088, 1 1 18, 1 124, 1 129, and 1 134; and

(3) a VH CDR3 having an amino acid sequence selected from the group consisting of SEQ ID NOS: 35, 1 1 19, 1 125, 1 130, 1415, and 1416; and/or

(b) a light chain variable (VL) region comprising:

(1 ) a VL CDR1 having an amino acid sequence selected from the group consisting of SEQ ID NOS: 42, 1 120, 1 126, and 1 131 ;

(2) a VL CDR2 having an amino acid sequence selected from the group consisting of SEQ ID NOS: 43, 1 121 , and 1 132; and

(3) a VL CDR3 having an amino acid sequence selected from the group consisting of SEQ ID NOS: 44, 1 127, and 1 133.

31 . The antibody of claim 30, wherein the antibody is humanized.

32. The antibody of claim 30 or 31 , wherein the VH region further comprises:

(1 ) a VH FR1 having an amino acid sequence selected from the group consisting of SEQ ID NOS: 51 , 39, 105, 58, 55, 1 15-121 , and 895-902;

(2) a VH FR2 having an amino acid sequence selected from the group consisting of SEQ ID NOS: 52, 106, 56, and 122-124;

(3) a VH FR3 having an amino acid sequence selected from the group consisting of SEQ ID NOS: 53, 107-1 13, 859-882, 57, 125-251 , and 903-1030; and/or

(4) a VH FR4 having an amino acid sequence of SEQ ID NO: 54.

33. The antibody of claim 30 or 31 , wherein the VL region further comprises:

a VL FR1 having an amino acid sequence selected from the group consisting of SEQ ID NOS: 91 , 1031 -1037, 79, and 1059-1061 ;

(2) a VL FR2 having an amino acid sequence selected from the group consisting of SEQ ID NOS: 92, 1038-1044, 80, 284, and 1062-1067;

(3) a VL FR3 having an amino acid sequence selected from the group consisting of SEQ ID NOS: 93, 1049-1055, 81 , 1068, 285, and 1069; and/or

(4) a VL FR4 having an amino acid sequence of SEQ ID NO: 78.

34. The antibody of claim 30 or 31 , wherein the antibody comprises a VH region and a VL region, wherein the VH region further comprises:

(1 ) a VH FR1 having an amino acid sequence selected from the group consisting of SEQ ID NOS: 51 , 39, 105, 58, 55, 1 15-121 , and 895-902;

(2) a VH FR2 having an amino acid sequence selected from the group consisting of SEQ ID NOS: 52, 106, 56, and 122-124;

(3) a VH FR3 having an amino acid sequence selected from the group consisting of SEQ ID NOS: 53, 107-1 13, 859-882, 57, 125-251 , and 903-1030; and/or

(4) a VH FR4 having an amino acid sequence of SEQ ID NO: 54; and wherein the VL region further comprises:

(1 ) a VL FR1 having an amino acid sequence selected from the group consisting of SEQ ID NOS: 91 , 1031 -1037, 79, and 1059-1061 ;

(2) a VL FR2 having an amino acid sequence selected from the group consisting of SEQ ID NOS: 92, 1038-1044, 80, 284, and 1062-1067;

(3) a VL FR3 having an amino acid sequence selected from the group consisting of SEQ ID NOS: 93, 1049-1055, 81 , 1068, 285, and 1069; and/or

(4) a VL FR4 having an amino acid sequence of SEQ ID NO: 78.

35. The antibody of any one of claims 29-34, wherein the antibody comprises:

(a) a VH region comprising:

(1 ) a VH CDR1 having an amino acid sequence of SEQ ID NO: 33, 1 1 17, 1 122, 1 123, or 1 128;

(2) a VH CDR2 having an amino acid sequence of SEQ ID NO: 34, 1082, 1088, 1 129, or 1 134; and

(3) a VH CDR3 having an amino acid sequence of SEQ ID NO: 35, 1415,

1 125, or 1416;

and/or

(b) a VL region comprising:

(1 ) a V|_ CDR1 having an amino acid sequence of SEQ ID NO: 42, 1 120,

1 126, or 1 131 ;

(2) a V|_ CDR2 having an amino acid sequence of SEQ ID NO: 43, 1 121 , or 1 132; and

(3) a VL CDR3 having an amino acid sequence of SEQ ID NO: 44, 1 127, or 1 133.

36. An isolated antibody that binds to a first group of C10orf54 proteins or

chimeric proteins designated CC1 (SEQ ID NO: 1079), CC3 (SEQ ID NO: 1244), CC4 (SEQ ID NO: 1245), CC5 (SEQ ID NO: 1246), CC8 (SEQ ID NO: 1249), and CC9 (SEQ ID NO: 1250), and does not bind to a second groupd of C10orf54 proteins or chimeric proteins designated CC2 (SEQ ID NO: 1243), CC6 (SEQ ID NO: 1247), CC7 (SEQ ID NO: 1248), and CC10 (SEQ ID NO: 1251 ).

37. The antibody of claim 36, wherein the antibody comprises:

(a) a VH region comprising:

(1 ) a VH CDR1 having an amino acid sequence of SEQ ID NO: 1326,

1327, 1328, 1329, or 1330;

(2) a VH CDR2 having an amino acid sequence of SEQ ID NO: 1375,

1376, 1377, 1378, or 1379; and

(3) a VH CDR3 having an amino acid sequence of SEQ ID NO: 1417,

1418, 1419, or 1420;

and/or

(b) a VL region comprising:

(1 ) a VL CDR1 having an amino acid sequence of SEQ ID NO: 1466, 1467, or 1468;

(2) a VL CDR2 having an amino acid sequence of SEQ ID NO: 1488, 1489, or 1490; and

(3) a VL CDR3 having an amino acid sequence of SEQ ID NO: 1517, 1518, or 1519.

38. The antibody of claim 37, wherein the antibody is humanized.

39. An isolated antibody that binds to a first group of C10orf54 proteins or

chimeric proteins designated CC1 (SEQ ID NO: 1079), CC4 (SEQ ID NO: 1245), CC5 (SEQ ID NO: 1246), CC8 (SEQ ID NO: 1249), and CC10 (SEQ ID NO: 1251 ), and does not bind to a second groupd of C10orf54 proteins or chimeric proteins designated CC2 (SEQ ID NO: 1243), CC3 (SEQ ID NO: 1244), CC6 (SEQ ID NO: 1247), CC7 (SEQ ID NO: 1248), CC9 (SEQ ID NO: 1250), and CC10 (SEQ ID NO: 1251 ).

40. The antibody of claim 39, wherein the antibody comprises:

(a) a VH region comprising:

(1 ) a VH CDR1 having an amino acid sequence of SEQ ID NO: 1331 ,

1332, 1333, 1334, or 1335;

(2) a VH CDR2 having an amino acid sequence of SEQ ID NO: 1380,

1381 , 1382, 1383, or 1384; and

(3) a VH CDR3 having an amino acid sequence of SEQ ID NO: 1421 ,

1422, 1423, or 1424;

and/or

(b) a VL region comprising:

(1 ) a VL CDR1 having an amino acid sequence of SEQ ID NO: 1469, 1470, 1471 , or 1472;

(2) a VL CDR2 having an amino acid sequence of SEQ ID NO: 1491 , 1488, or 1492; and

(3) a VL CDR3 having an amino acid sequence of SEQ ID NO: 1520, 1521 , or 1522.

41 The antibody of claim 40, wherein the antibody is humanized.

42. An isolated antibody that binds to C10orf54, wherein the antibody comprises:

(a) a heavy chain variable (VH) region comprising:

(1 ) a VH CDR1 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is selected from the group consisting of SEQ ID NOS:36, 30, 59-62, and 33;

(2) a VH CDR2 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is selected from the group consisting of SEQ ID NOS:37, 101 -104, 50, 1 14, 99, 100, 31 , 65-74, 83-90, 95, 321 , 322, 835-842, 34, 847-858, 49, 886-894, and 1070-1078; and

(3) a VH CDR3 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is selected from the group consisting of SEQ ID NOS:38, 32, 319, 35, and 883-885;

and/or

(b) a light chain variable (VL) region comprising:

(1 ) a VL CDR1 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is selected from the group consisting of SEQ ID NOS:45, 253-271 , and 42;

(2) a VL CDR2 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is selected from the group consisting of SEQ ID NOS:46, 272-275, 40, 843-846, 43, and 1045-1048; and

(3) a VL CDR3 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is selected from the group consisting of SEQ ID NOS:47, 41 , 44, and 1056-1058.

43. The antibody of claim 42, wherein the antibody is humanized.

44. The antibody of claim 42 or 43, wherein the VH region further comprises:

(1 ) a VH FR1 having an amino acid sequence derived from or based on a human VH germ line sequence selected from the group consisting of IGHV1 -18, IGHV1 -46, IGHV3-74, IGHV4-61 or a VH FR1 having an amino acid sequence selected from the group consisting of SEQ ID NOS:51 , 105, 55, 1 15-121 , 39, 58, and 895-902;

(2) a VH FR2 having an amino acid sequence derived from or based on a human VH germ line sequence selected from the group consisting of

IGHV1 -18, IGHV1 -46, IGHV3-74, IGHV4-61 or a VH FR2 having an amino acid sequence selected from the group consisting of SEQ ID NOS:52, 106, 56, 122-124, 63, 64, and 323-326;

(3) a VH FR3 having an amino acid sequence derived from or based on a human VH germ line sequence selected from the group consisting of

IGHV1 -18, IGHV1 -46, IGHV3-74, IGHV4-61 or a VH FR3 having an amino acid sequence selected from the group consisting of SEQ ID NOS:53, 107-1 13, 57, 125-251 , 96-98, 292-318, 327-833, 53, 859-882, and 903-1030; and/or

(4) a VH FR4 having an amino acid sequence derived from or based on a human VH germ line sequence selected from the group consisting of IGHV1 -18, IGHV1 -46, IGHV3-74, IGHV4-61 or a VH FR4 having an amino acid sequence of SEQ ID NO:54, 320, 1680.

45. The antibody of claim 42 or 43, wherein the VL region further comprises:

(1 ) a V|_ FR1 having an amino acid sequence derived from or based on a human VL germ line sequence selected from the group consisting of IGKV1 -39, IGKV3-1 1 , IGKV4-1 , IGKV3D-20, IGKV2-30, IGKV2-28, IGKV2-29, IGKV3-20 or a VL FR1 selected from the group consisting of SEQ ID NOS:75, 252, 79, 277-283, 91 , 1031 -1037, and 1059-1061 ; (2) a V|_ FR2 having an amino acid sequence derived from or based on a human VL germ line sequence selected from the group consisting of IGKV1 -39, IGKV3-1 1 , IGKV4-1 , IGKV3D-20, IGKV2-30, IGKV2-28, IGKV2-29, IGKV3-20 or a VL FR2 selected from the group consisting of SEQ ID NOS:76, 80, 284, 92, 1038-1044, and 1062-1067; (3) a VL FR3 having an amino acid sequence derived from or based on a human VL germ line sequence selected from the group consisting of IGKV1 -39, IGKV3-1 1 , IGKV4-1 , IGKV3D-20, IGKV2-30, IGKV2-28, IGKV2-29, IGKV3-20 or a VL FR3 selected from the group consisting of SEQ ID NOS:77, 276, 81 , 285-291 , 93, 1049-1055, 1068, and 1069; and/or

(4) a VL FR4 having an amino acid sequence derived from or based on a human VL germ line sequence selected from the group consisting of IGKV1 -39, IGKV3-1 1 , IGKV4-1 , IGKV3D-20, IGKV2-30, IGKV2-28, IGKV2-29, IGKV3-20 or a VL FR4 having an amino acid of SEQ ID NO:78.

46. The antibody of claim 42 or 43, wherein the antibody comprises a VH region and a VL region, wherein the VH region further comprises:

(1 ) a VH FR1 having an amino acid sequence derived from or based on a human VH germ line sequence selected from the group consisting of IGHV1 -18, IGHV1 -46, IGHV3-74, IGHV4-61 or a VH FR1 having an amino acid sequence selected from the group consisting of SEQ ID NOS:51 , 105, 55, 1 15-121 , 39, 58, and 895-902;

(2) a VH FR2 having an amino acid sequence derived from or based on a human VH germ line sequence selected from the group consisting of IGHV1 -18, IGHV1 -46, IGHV3-74, IGHV4-61 or a VH FR2 having an amino acid sequence selected from the group consisting of SEQ ID NOS:52, 106, 56, 122-124, 63, 64, and 323-326;

(3) a VH FR3 having an amino acid sequence derived from or based on a human VH germ line sequence selected from the group consisting of IGHV1 -18, IGHV1 -46, IGHV3-74, IGHV4-61 or a VH FR3 having an amino acid sequence selected from the group consisting of SEQ ID NOS:53, 107-1 13, 57, 125-251 , 96-98, 292-318, 327-833, 53, 859-882, and 903-1030; and/or

(4) a VH FR4 having an amino acid sequence derived from or based on a human VH germ line sequence selected from the group consisting of IGHV1 -18, IGHV1 -46, IGHV3-74, IGHV4-61 or a VH FR4 having an amino acid sequence of SEQ ID NO:54, 320, 1680; and

wherein the VL region further comprises:

(1 ) a VL FR1 having an amino acid sequence derived from or based on a human VL germ line sequence selected from the group consisting of IGKV1 -39, IGKV3-1 1 , IGKV4-1 , IGKV3D-20, IGKV2-30, IGKV2-28, IGKV2-29, IGKV3-20 or a VL FR1 selected from the group consisting of SEQ ID NOS:75, 252, 79, 277-283, 91 , 1031 -1037, and 1059-1061 ; (2) a VL FR2 having an amino acid sequence derived from or based on a human VL germ line sequence selected from the group consisting of IGKV1 -39, IGKV3-1 1 , IGKV4-1 , IGKV3D-20, IGKV2-30, IGKV2-28, IGKV2-29, IGKV3-20 or a VL FR2 selected from the group consisting of SEQ ID NOS:76, 80, 284, 92, 1038-1044, and 1062-1067;

(3) a VL FR3 having an amino acid sequence derived from or based on a human VL germ line sequence selected from the group consisting of IGKV1 -39, IGKV3-1 1 , IGKV4-1 , IGKV3D-20, IGKV2-30, IGKV2-28, IGKV2-29, IGKV3-20 or a VL FR3 selected from the group consisting of SEQ ID NOS:77, 276, 81 , 285-291 , 93, 1049-1055, 1068, and 1069; and/or

(4) a VL FR4 having an amino acid sequence derived from or based on a human VL germ line sequence selected from the group consisting of IGKV1 -39, IGKV3-1 1 , IGKV4-1 , IGKV3D-20, IGKV2-30, IGKV2-28, IGKV2-29, IGKV3-20 or a VL FR4 having an amino acid of SEQ ID

NO:78.

47. The antibody of any one of claims 42 to 46, wherein the antibody comprises:

(a) a VH region comprising:

(1 ) a VH CDR1 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is SEQ ID NO:36;

(2) a VH CDR2 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is selected from the group consisting of SEQ ID NOS:37, 101 -104, 50, 1 14, 99, and 100; and

(3) a VH CDR3 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is SEQ ID NO:38;

and

(b) a VL region comprising:

(1 ) a VL CDR1 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is selected from the group consisting of SEQ ID NOS:45, and 253-271 ;

(2) a VL CDR2 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is selected from the group consisting of SEQ ID NOS:46, and 272-275; and

(3) a VL CDR3 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is SEQ ID NO:47.

The antibody of claim 47, wherein the VH region further comprises:

(1 ) a VH FR1 having an amino acid sequence derived from or based on a human VH germ line sequence selected from the group consisting of IGHV1 -18, IGHV1 -46, IGHV3-74, IGHV4-61 or a VH FR1 having an amino acid sequence selected from the group consisting of SEQ ID NOS: 51 , 105, 55, and 1 15-121 ;

(2) a VH FR2 having an amino acid sequence derived from or based on a human VH germ line sequence selected from the group consisting of IGHV1 -18, IGHV1 -46, IGHV3-74, IGHV4-61 or a VH FR2 having an amino acid sequence selected from the group consisting of SEQ ID NOS: 52, 106, 56, and 122-124;

(3) a VH FR3 having an amino acid sequence derived from or based on a human VH germ line sequence selected from the group consisting of IGHV1 -18, IGHV1 -46, IGHV3-74, IGHV4-61 or a VH FR3 having an amino acid sequence selected from the group consisting of SEQ ID NOS: 53, 107-1 13, 57, and 125-251 ; and/or

(4) a VH FR4 having an amino acid sequence derived from or based on a human VH germ line sequence selected from the group consisting of IGHV1 -18, IGHV1 -46, IGHV3-74, IGHV4-61 or a VH FR4 having an amino acid sequence of SEQ ID NO:54.

The antibody of claim 47 or 48, wherein the VL region further comprises:

(1 ) a VL FR1 having an amino acid sequence derived from or based on a human VL germ line sequence selected from the group consisting of IGKV1 -39, IGKV3-1 1 , IGKV4-1 , IGKV3D-20, IGKV2-30, IGKV2-28, IGKV2-29, IGKV3-20 or a VL FR1 selected from the group consisting of SEQ ID NOS: 75, 252, 79, and 277-283;

(2) a VL FR2 having an amino acid sequence derived from or based on a human VL germ line sequence selected from the group consisting of IGKV1 -39, IGKV3-1 1 , IGKV4-1 , IGKV3D-20, IGKV2-30, IGKV2-28, IGKV2-29, IGKV3-20 or a VL FR2 selected from the group consisting of SEQ ID NOS: 76, 80, and 284;

(3) a VL FR3 having an amino acid sequence derived from or based on a human VL germ line sequence selected from the group consisting of IGKV1 -39, IGKV3-1 1 , IGKV4-1 , IGKV3D-20, IGKV2-30, IGKV2-28, IGKV2-29, IGKV3-20 or a VL FR3 selected from the group consisting of SEQ ID NOS: 77, 276, 81 , and 285-291 ; and/or

(4) a VL FR4 having an amino acid sequence derived from or based on a human VL germ line sequence selected from the group consisting of IGKV1 -39, IGKV3-1 1 , IGKV4-1 , IGKV3D-20, IGKV2-30, IGKV2-28, IGKV2-29, IGKV3-20 or a VL FR4 having an amino acid of SEQ ID NO:78.

50. The antibody of any one of claims 42 to 47, wherein the antibody comprises:

(a) a VH region comprising:

(1 ) a VH CDR1 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is SEQ ID NO:36;

(2) a VH CDR2 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is SEQ ID NO:37; and

(3) a VH CDR3 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is SEQ ID NO:38;

and

(b) a VL region comprising:

(1 ) a VL CDR1 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is SEQ ID NO:45;

(2) a VL CDR2 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is SEQ ID NO:46; and

(3) a VL CDR3 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is SEQ ID NO:47.

The antibody of any one of claims 42 to 47, wherein the antibody comprises:

(a) a VH region comprising:

(1 ) a VH CDR1 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is SEQ ID NO:36;

(2) a VH CDR2 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is SEQ ID NO:50; and

(3) a VH CDR3 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is SEQ ID NO:38;

and

(b) a VL region comprising:

(1 ) a VL CDR1 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is SEQ ID NO:45;

(2) a VL CDR2 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is SEQ ID NO:46; and

(3) a VL CDR3 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is SEQ ID NO:47.

The antibody of any one of claims 42 to 47, wherein the antibody comprises:

(a) a VH region comprising:

(1 ) a VH CDR1 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is SEQ ID NO:36;

(2) a VH CDR2 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is SEQ ID NO:99; and

(3) a VH CDR3 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is SEQ ID NO:38;

and

(b) a VL region comprising:

(1 ) a VL CDR1 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is SEQ ID NO:45;

(2) a VL CDR2 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is SEQ ID NO:46; and

(3) a V|_ CDR3 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is SEQ ID NO:47.

53. The antibody of any one of claims 42 to 52, wherein the VH region comprises the amino acid sequence as shown in Tables 12-33 except for a sequence that is SEQ ID NO:20, 21 , 22 or 23.

54. The antibody of any one of claims 42 to 53, wherein the VL region comprises the amino acid sequence as shown in Tables 12-33 except for a sequence that is SEQ ID NO:28 or 29.

55. The antibody of any one of claims 42 to 46, wherein the antibody comprises:

(a) a VH region comprising:

(1 ) a VH CDR1 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is selected from the group consisting of SEQ ID NOS:30 and 59-62;

(2) a VH CDR2 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is selected from the group consisting of SEQ ID NOS:31 , 65-74, 83-90, 95, 321 , 322, and 835-842; and

(3) a VH CDR3 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is SEQ ID NO:32 or 319;

and

(b) a VL region comprising:

(1 ) a VL CDR1 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is selected from the group consisting of SEQ ID NOS:45, and 253-271 ;

(2) a VL CDR2 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is selected from the group consisting of SEQ ID NOS:40, and 843-846; and

(3) a VL CDR3 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is SEQ ID NO:41 .

56. The antibody of claim 55, wherein the VH region further comprises:

(1 ) a VH FR1 having an amino acid sequence derived from or based on a human VH germ line sequence selected from the group consisting of IGHV1 -18, IGHV1 -46, IGHV3-74, IGHV4-61 or a VH FR1 having an amino acid sequence selected from the group consisting of SEQ ID NOS: 51 , 105, 55, and 1 15-121 ;

(2) a VH FR2 having an amino acid sequence derived from or based on a human VH germ line sequence selected from the group consisting of IGHV1 -18, IGHV1 -46, IGHV3-74, IGHV4-61 or a VH FR2 having an amino acid sequence selected from the group consisting of SEQ ID NOS: 52, 106, 63, 64, 56, 122-124, and 323-326;

(3) a VH FR3 having an amino acid sequence derived from or based on a human VH germ line sequence selected from the group consisting of IGHV1 -18, IGHV1 -46, IGHV3-74, IGHV4-61 or a VH FR3 having an amino acid sequence selected from the group consisting of SEQ ID NOS: 53, 107, 96-98, 292-318, 57, and 327-833; and/or

(4) a VH FR4 having an amino acid sequence derived from or based on a human VH germ line sequence selected from the group consisting of IGHV1 -18, IGHV1 -46, IGHV3-74, IGHV4-61 or a VH FR4 having an amino acid sequence of SEQ ID NO:54, 320, 1680.

57. The antibody of claim 55 or 56, wherein the VL region further comprises:

(1 ) a VL FR1 having an amino acid sequence derived from or based on a human VL germ line sequence selected from the group consisting of IGKV1 -39, IGKV3-1 1 , IGKV4-1 , IGKV3D-20, IGKV2-30, IGKV2-28, IGKV2-29, IGKV3-20 or a VL FR1 selected from the group consisting of SEQ ID NOS: 75, 252, 79, and 277-283;

(2) a VL FR2 having an amino acid sequence derived from or based on a human VL germ line sequence selected from the group consisting of IGKV1 -39, IGKV3-1 1 , IGKV4-1 , IGKV3D-20, IGKV2-30, IGKV2-28, IGKV2-29, IGKV3-20 or a VL FR2 selected from the group consisting of SEQ ID NOS: 76, 80, and 284;

(3) a VL FR3 having an amino acid sequence derived from or based on a human VL germ line sequence selected from the group consisting of IGKV1 -39, IGKV3-1 1 , IGKV4-1 , IGKV3D-20, IGKV2-30, IGKV2-28, IGKV2-29, IGKV3-20 or a VL FR3 selected from the group consisting of SEQ ID NOS: 77, 276, 81 , and 285-291 ; and/or

(4) a VL FR4 having an amino acid sequence derived from or based on a human VL germ line sequence selected from the group consisting of IGKV1 -39, IGKV3-1 1 , IGKV4-1 , IGKV3D-20, IGKV2-30, IGKV2-28, IGKV2-29, IGKV3-20 or a VL FR4 having an amino acid of SEQ ID NO:78.

58. The antibody of any one of claims 42 to 47 or 55 to 57, wherein the antibody comprises:

(a) a VH region comprising:

(1 ) a VH CDR1 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is SEQ ID NO:30;

(2) a VH CDR2 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is SEQ ID NO:31 ; and

(3) a VH CDR3 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is SEQ ID NO:32;

and

(b) a VL region comprising:

(1 ) a VL CDR1 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is SEQ ID NO:45;

(2) a VL CDR2 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is SEQ ID NO:40; and

(3) a VL CDR3 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is SEQ ID NO:41 .

59. The antibody of any one of claims 42 to 47 or 55 to 58, wherein the antibody comprises:

(a) a VH region comprising:

(1 ) a VH CDR1 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is SEQ ID NO:30;

(2) a VH CDR2 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is SEQ ID NO:321 ; and

(3) a VH CDR3 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is SEQ ID NO:32;

and

(b) a VL region comprising:

(1 ) a VL CDR1 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is SEQ ID NO:45;

(2) a VL CDR2 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is SEQ ID NO:40; and

(3) a VL CDR3 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is SEQ ID NO:41 .

60. The antibody of any one of claims 42 to 47 or 55 to 58, wherein the antibody comprises:

(a) a VH region comprising:

(1 ) a VH CDR1 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is SEQ ID NO:30;

(2) a VH CDR2 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is SEQ ID NO:835; and

(3) a VH CDR3 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is SEQ ID NO:32;

and

(b) a VL region comprising:

(1 ) a VL CDR1 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is SEQ ID NO:45;

(2) a VL CDR2 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is SEQ ID NO:40; and

(3) a VL CDR3 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is SEQ ID NO:41 .

61 . The antibody of any one of claims 42 to 47 or 55 to 58, wherein the VH region comprises the amino acid sequence as shown in Tables 12-33 except for a sequence that is SEQ ID NO: 12, 13, 14 or 15.

62. The antibody of any one of claims 42 to 47 or 55 to 58, wherein the VL region comprises the amino acid sequence as shown in Tables 12-33 except for a sequence that is SEQ ID NO:24 or 25.

63. The antibody of any one of claims 42 to 47, wherein the antibody comprises:

(a) a VH region comprising:

(1 ) a VH CDR1 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is SEQ ID NO:33;

(2) a VH CDR2 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is selected from the group consisting of SEQ ID NOS:34, 847-858, 49, 886-894, 99 and 1070-1078; and

(3) a VH CDR3 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is selected from the group consisting of SEQ ID NOS:35 and 883-885;

and

(b) a VL region comprising:

(1 ) a VL CDR1 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is SEQ ID NO:42;

(2) a VL CDR2 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is selected from the group consisting of SEQ ID NOS:43 and 1045-1048; and

(3) a VL CDR3 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is selected from the group consisting of SEQ ID NOS:44 and 1056-1058.

64. The antibody of claim 63, wherein the VH region further comprises:

(1 ) a VH FR1 having an amino acid sequence derived from or based on a human VH germ line sequence selected from the group consisting of IGHV1 -18, IGHV1 -46, IGHV3-74, IGHV4-61 or a VH FR1 having an amino acid sequence selected from the group consisting of SEQ ID NOS: 51 , 39, 105, 58, 55, 1 15-121 , and 895-902;

(2) a VH FR2 having an amino acid sequence derived from or based on a human VH germ line sequence selected from the group consisting of

IGHV1 -18, IGHV1 -46, IGHV3-74, IGHV4-61 or a VH FR2 having an amino acid sequence selected from the group consisting of SEQ ID NOS: 52, 106, 56, and 122-124;

(3) a VH FR3 having an amino acid sequence derived from or based on a human VH germ line sequence selected from the group consisting of IGHV1 -18, IGHV1 -46, IGHV3-74, IGHV4-61 or a VH FR3 having an amino acid sequence selected from the group consisting of SEQ ID NOS: 53, 107-1 13, 57, 859-882, 125-251 ; and/or

(4) a VH FR4 having an amino acid sequence derived from or based on a human VH germ line sequence selected from the group consisting of IGHV1 -18, IGHV1 -46, IGHV3-74, IGHV4-61 or a VH FR4 having an amino acid sequence of SEQ ID NO:54.

65. The antibody of claim 63 or 64, wherein the VL region further comprises:

(1 ) a VL FR1 having an amino acid sequence derived from or based on a human VL germ line sequence selected from the group consisting of

IGKV1 -39, IGKV3-1 1 , IGKV4-1 , IGKV3D-20, IGKV2-30, IGKV2-28, IGKV2-29, IGKV3-20 or a VL FR1 selected from the group consisting of SEQ ID NOS: 91 , 1031 -1037, and 1059-1061 ;

(2) a VL FR2 having an amino acid sequence derived from or based on a human VL germ line sequence selected from the group consisting of

IGKV1 -39, IGKV3-1 1 , IGKV4-1 , IGKV3D-20, IGKV2-30, IGKV2-28, IGKV2-29, IGKV3-20 or a VL FR2 selected from the group consisting of SEQ ID NOS: 92, 1038-1044, 80, 284 and 1062-1067;

(3) a VL FR3 having an amino acid sequence derived from or based on a human VL germ line sequence selected from the group consisting of

IGKV1 -39, IGKV3-1 1 , IGKV4-1 , IGKV3D-20, IGKV2-30, IGKV2-28, IGKV2-29, IGKV3-20 or a VL FR3 selected from the group consisting of SEQ ID NOS: 81 , 285, 93, 1049-1055, 1068, and 1069; and/or

(4) a VL FR4 having an amino acid sequence derived from or based on a human VL germ line sequence selected from the group consisting of

IGKV1 -39, IGKV3-1 1 , IGKV4-1 , IGKV3D-20, IGKV2-30, IGKV2-28, IGKV2-29, IGKV3-20 or a VL FR4 having an amino acid of SEQ ID NO:78.

66. The antibody of any one of claims 42 to 47 or 63 to 65, wherein the antibody comprises:

(a) a VH region comprising:

(1 ) a VH CDR1 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is SEQ ID NO:33;

(2) a VH CDR2 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is SEQ ID NO:34; and

(3) a VH CDR3 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is SEQ ID NO:35;

and

(b) a VL region comprising:

(1 ) a VL CDR1 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is SEQ ID NO:42;

(2) a VL CDR2 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is SEQ ID NO:43; and

(3) a VL CDR3 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is SEQ ID NO:44.

67. The antibody of any one of claims 42 to 47 or 63 to 65, wherein the antibody comprises:

(a) a VH region comprising:

(1 ) a VH CDR1 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is SEQ ID NO:33;

(2) a VH CDR2 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is SEQ ID NO:49; and

(3) a VH CDR3 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is SEQ ID NO:35;

and

(b) a VL region comprising:

(1 ) a VL CDR1 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is SEQ ID NO:42;

(2) a VL CDR2 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is SEQ ID NO:43; and

(3) a VL CDR3 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is SEQ ID NO:44.

68. The antibody of any one of claims 42 to 47 or 63 to 65, wherein the antibody comprises:

(a) a VH region comprising:

(1 ) a VH CDR1 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is SEQ ID NO:33;

(2) a VH CDR2 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is SEQ ID NO: 1070; and

(3) a VH CDR3 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is SEQ ID NO:35;

and

(b) a VL region comprising:

(1 ) a VL CDR1 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is SEQ ID NO:42;

(2) a VL CDR2 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is SEQ ID NO:43; and

(3) a VL CDR3 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is SEQ ID NO:44.

69. The antibody of any one of claims 42 to 47 or 63 to 65, wherein the VH region comprises the amino acid sequence as shown in Tables 12-33 except for a sequence that is SEQ ID NO: 16, 17, 18 or 19.

70. The antibody of any one of claims 42 to 47 or 63 to 65, wherein the VL region comprises the amino acid sequence as shown in Tables 12-33 except for a sequence that is SEQ ID NO:26 or 27.

71 . An isolated antibody that binds to C10orf54, wherein the antibody comprises:

(a) a heavy chain variable (VH) region comprising:

(1) a VH CDR1 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is selected from the group consisting of SEQ ID NOS: 36, 1081, 1086, 1087, 1092, 30, 1099, 1104, 1105, 1110, 33, 1117, 1122, 1123 and 1128;

(2) a VH CDR2 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is selected from the group consisting of SEQ ID NOS: 37, 1082, 1088, 1093, 1098, 31 , 1100, 1106, 1111 , 1116, 34, 1118, 1124, 1129 and 1134; and

(3) a VH CDR3 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is selected from the group consisting of

SEQ ID NOS: 38, 1083, 1089, 1094, 32, 1101 , 1107, 1112, 35, 1119, 1125 and 1130;

and/or

(b) a light chain variable (VL) region comprising:

(1) a VL CDR1 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is selected from the group consisting of SEQ ID NOS: 45, 1084, 1090, 1095, 1102, 1108, 1113, 42, 1120, 1126 and 1131;

(2) a VL CDR2 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is selected from the group consisting of

SEQ ID NOS: 46, 1085, 1096, 40, 1103, 1114, 43, 1121 and 1132; and

(3) a VL CDR3 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is selected from the group consisting of SEQ ID NOS: 47, 1091, 1097, 41, 1109, 1115, 44, 1127 and 1133.

72. The isolated antibody of claim 71 , wherein the antibody comprises:

(a) a heavy chain variable (VH) region comprising:

(1) a VH CDR1 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is SEQ ID NO: 1081 ;

(2) a VH CDR2 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is SEQ ID NO: 1082; and

(3) a VH CDR3 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is SEQ ID NO: 1083;

and

(b) a light chain variable (VL) region comprising:

(1 ) a VL CDR1 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is SEQ ID NO: 1084;

(2) a VL CDR2 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is SEQ ID NO: 1085; and

(3) a VL CDR3 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is SEQ ID NO: 47.

The isolated antibody of claim 71 , wherein the antibody comprises:

(a) a heavy chain variable (VH) region comprising:

(1 ) a VH CDR1 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is SEQ ID NO: 1086;

(2) a VH CDR2 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is SEQ ID NO: 37; and

(3) a VH CDR3 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is SEQ ID NO: 38;

and

(b) a light chain variable (VL) region comprising:

(1 ) a VL CDR1 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is SEQ ID NO: 45;

(2) a VL CDR2 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is SEQ ID NO: 46; and

(3) a VL CDR3 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is SEQ ID NO: 47.

The isolated antibody of claim 71 , wherein the antibody comprises:

(a) a heavy chain variable (VH) region comprising:

(1 ) a VH CDR1 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is SEQ ID NO: 1087;

(2) a VH CDR2 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is SEQ ID NO: 1088; and

(3) a VH CDR3 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is SEQ ID NO: 1089;

and

(b) a light chain variable (VL) region comprising:

(1 ) a VL CDR1 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is SEQ ID NO: 1090;

(2) a VL CDR2 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is SEQ ID NO: 1085; and

(3) a VL CDR3 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is SEQ ID NO: 1091 .

The isolated antibody of claim 71 , wherein the antibody comprises:

(a) a heavy chain variable (VH) region comprising:

(1 ) a VH CDR1 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is SEQ ID NO: 1092;

(2) a VH CDR2 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is SEQ ID NO: 1093; and

(3) a VH CDR3 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is SEQ ID NO: 1094;

and

(b) a light chain variable (VL) region comprising:

(1 ) a VL CDR1 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is SEQ ID NO: 1095;

(2) a VL CDR2 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is SEQ ID NO: 1096; and

(3) a VL CDR3 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is SEQ ID NO: 1097.

The isolated antibody of claim 71 , wherein the antibody comprises:

(a) a heavy chain variable (VH) region comprising:

(1 ) a VH CDR1 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is SEQ ID NO: 36;

(2) a VH CDR2 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is SEQ ID NO: 1098; and

(3) a VH CDR3 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is SEQ ID NO: 38;

and

(b) a light chain variable (VL) region comprising:

(1 ) a VL CDR1 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is SEQ ID NO: 45;

(2) a VL CDR2 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is SEQ ID NO: 46; and

(3) a VL CDR3 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is SEQ ID NO: 47.

The isolated antibody of claim 71 , wherein the antibody comprises:

(a) a heavy chain variable (VH) region comprising:

(1 ) a VH CDR1 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is SEQ ID NO: 1099;

(2) a VH CDR2 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is SEQ ID NO: 1 100; and

(3) a VH CDR3 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is SEQ ID NO: 1 101 ;

and

(b) a light chain variable (VL) region comprising:

(1 ) a VL CDR1 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is SEQ ID NO: 1 102;

(2) a VL CDR2 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is SEQ ID NO: 1 103; and

(3) a VL CDR3 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is SEQ ID NO: 41 .

The isolated antibody of claim 71 , wherein the antibody comprises:

(a) a heavy chain variable (VH) region comprising:

(1 ) a VH CDR1 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is SEQ ID NO: 1 104;

(2) a VH CDR2 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is SEQ ID NO: 31 ; and

(3) a VH CDR3 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is SEQ ID NO: 32;

and

(b) a light chain variable (VL) region comprising:

(1 ) a VL CDR1 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is SEQ ID NO: 45;

(2) a VL CDR2 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is SEQ ID NO: 40; and

(3) a VL CDR3 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is SEQ ID NO: 41 .

The isolated antibody of claim 71 , wherein the antibody comprises:

(a) a heavy chain variable (VH) region comprising:

(1 ) a VH CDR1 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is SEQ ID NO: 1 105;

(2) a VH CDR2 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is SEQ ID NO: 1 106; and

(3) a VH CDR3 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is SEQ ID NO: 1 107;

and

(b) a light chain variable (VL) region comprising:

(1 ) a VL CDR1 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is SEQ ID NO: 1 108;

(2) a VL CDR2 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is SEQ ID NO: 1 103; and

(3) a VL CDR3 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is SEQ ID NO: 1 109.

The isolated antibody of claim 71 , wherein the antibody comprises:

(a) a heavy chain variable (VH) region comprising:

(1 ) a VH CDR1 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is SEQ ID NO: 1 1 10;

(2) a VH CDR2 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is SEQ ID NO: 1 1 1 1 ; and

(3) a VH CDR3 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is SEQ ID NO: 1 1 12;

and

(b) a light chain variable (VL) region comprising:

(1 ) a VL CDR1 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is SEQ ID NO: 1 1 13;

(2) a VL CDR2 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is SEQ ID NO: 1 1 14; and

(3) a VL CDR3 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is SEQ ID NO: 1 1 15.

The isolated antibody of claim 71 , wherein the antibody comprises:

(a) a heavy chain variable (VH) region comprising:

(1 ) a VH CDR1 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is SEQ ID NO: 30;

(2) a VH CDR2 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is SEQ ID NO: 1 1 16; and

(3) a VH CDR3 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is SEQ ID NO: 32;

and

(b) a light chain variable (VL) region comprising:

(1 ) a VL CDR1 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is SEQ ID NO: 45;

(2) a VL CDR2 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is SEQ ID NO: 40; and

(3) a VL CDR3 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is SEQ ID NO: 41 .

The isolated antibody of claim 71 , wherein the antibody comprises:

(a) a heavy chain variable (VH) region comprising:

(1 ) a VH CDR1 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is SEQ ID NO: 1 1 17;

(2) a VH CDR2 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is SEQ ID NO: 1 1 18; and

(3) a VH CDR3 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is SEQ ID NO: 1 1 19;

and

(b) a light chain variable (VL) region comprising:

(1 ) a VL CDR1 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is SEQ ID NO: 1 120;

(2) a VL CDR2 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is SEQ ID NO: 1 121 ; and

(3) a VL CDR3 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is SEQ ID NO: 44.

83. The isolated antibody of claim 71 , wherein the antibody comprises:

(a) a heavy chain variable (VH) region comprising:

(1 ) a VH CDR1 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is SEQ ID NO: 1 122;

(2) a VH CDR2 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is SEQ ID NO: 34; and

(3) a VH CDR3 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is SEQ ID NO: 35;

and

(b) a light chain variable (VL) region comprising:

(1 ) a VL CDR1 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is SEQ ID NO: 42;

(2) a VL CDR2 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is SEQ ID NO: 43; and

(3) a VL CDR3 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is SEQ ID NO: 44.

84. The isolated antibody of claim 71 , wherein the antibody comprises:

(a) a heavy chain variable (VH) region comprising:

(1 ) a VH CDR1 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is SEQ ID NO: 1 123;

(2) a VH CDR2 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is SEQ ID NO: 1 124; and

(3) a VH CDR3 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is SEQ ID NO: 1 125;

and

(b) a light chain variable (VL) region comprising:

(1 ) a VL CDR1 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is SEQ ID NO: 1 126;

(2) a VL CDR2 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is SEQ ID NO: 1 121 ; and

(3) a VL CDR3 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is SEQ ID NO: 1 127.

The isolated antibody of claim 71 , wherein the antibody comprises:

(a) a heavy chain variable (VH) region comprising:

(1 ) a VH CDR1 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is SEQ ID NO: 1 128;

(2) a VH CDR2 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is SEQ ID NO: 1 129; and

(3) a VH CDR3 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is SEQ ID NO: 1 130;

and

(b) a light chain variable (VL) region comprising:

(1 ) a VL CDR1 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is SEQ ID NO: 1 131 ;

(2) a VL CDR2 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is SEQ ID NO: 1 132; and

(3) a VL CDR3 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is SEQ ID NO: 1 133.

The isolated antibody of claim 71 , wherein the antibody comprises:

(a) a heavy chain variable (VH) region comprising:

(1 ) a VH CDR1 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is SEQ ID NO: 33;

(2) a VH CDR2 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is SEQ ID NO: 1 134; and

(3) a VH CDR3 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is SEQ ID NO: 35;

and

(b) a light chain variable (VL) region comprising:

(1 ) a VL CDR1 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is SEQ ID NO: 42;

(2) a VL CDR2 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is SEQ ID NO: 43; and

(3) a VL CDR3 having an amino acid sequence as shown in Tables 12-33 except for a sequence that is SEQ ID NO: 44.

87. The antibody of any one of claims 1 to 86, wherein the antibody is a

monoclonal antibody.

88. The antibody of any one of claims 1 to 86, wherein the antibody is a

recombinant antibody or a fusion protein.

89. The antibody of any one of claims 1 to 86, wherein the antibody is an antigen binding fragment.

90. The antibody of any one of claims 1 to 86, wherein the antibody is a Fab Fragment, F(ab')2 fragment, single chain Fv (sFv), diabody, triabody, or minibody.

91 . An isolated antibody that binds to a C10orf54 epitope, wherein the binding to the epitope competitively blocks the binding of the antibody of any one of claims 1 to 90 in a dose-dependent manner.

92. An antibody of any one of claims 1 to 91 , wherein the antibody is conjugated or recombinantly fused to a diagnostic agent, detectable agent or therapeutic agent.

93. The antibody of claim 92, wherein the therapeutic agent is a

chemotherapeutic agent.

The antibody of claim 92, wherein the therapeutic agent is a cytotoxin

95. The antibody of claim 92, wherein the antibody is conjugated to a detectable agent.

96. The antibody of any one of claims 92 to 95, wherein the conjugation comprises a linker of the following formula

(L1 )a-(L2)b-(L3)c .

wherein:

L1 , L2 and L3 is independently a linker selected from the group consisting of

-0-, -C(O)-, -S-, -S(O)-, -S(O)2- -NH-, -NCHs-, -(CH2)q- -NH(CH2)2NH-, -OC(O)-, -C02- -NHCH2CH2C(0)-, -C(0)NHCH2CH2NH-, -NHCH2C(0)-, -NHC(O)-, -C(0)NH-, -NCH3C(0)-, -C(O)NCH3- -(CH2CH20)p,

-(CH2CH20)pCH2CH2-, -CH2CH2-(CH2CH20)p- -OCH(CH20-)2, -(AA)r- cyclopentanyl, cyclohexanyl, unsubstituted phenylenyl, and phenylenyl substituted by 1 or 2 substituents selected from the group consisting of halo, CF3-, CF3O-, CH3O-, -C(0)OH, -C(0)OC1 -3 alkyl, -C(0)CH3, -CN, -NH2, -OH, NHCH3, -N(CH3)2, and Ci-3 alkyl.

97. A composition comprising the antibody of any one of claims 1 to 96.

98. The composition of claim 97, wherein the composition is a pharmaceutical composition comprising a pharmaceutically acceptable carrier or excipient.

99. An isolated nucleic acid molecule comprising or consisting of a nucleic acid sequence that encodes the VH region or VL region of any one of claims 1 to 91 .

100. A vector comprising the nucleic acid molecule of claim 99.

101 . A host cell comprising the vector of claim 100.

102. A method of producing an antibody comprising culturing the host cell of claim 101 under conditions that promotes the production of the antibody.

103. A method of treating, preventing or alleviating one or more symptoms of a disease comprising administering a therapeutically effective amount of the composition of claim 97 or 98 to a subject, thereby treating, preventing or alleviating one or more symptoms of the disease.

104. The method of claim 103, wherein the disease is a cancer.

105. The method of claim 104, wherein the cancer is a leukemia, a bladder cancer, a skin cancer, a colon cancer, a breast cancer, a liver cancer, a kidney cancer, a lung cancer, a stomach cancer, a pancreas cancer, an esophagus canceror a fibrosarcoma.

106. The method of claim 105, wherein the leukemia is an acute myeloid leukemia (AML).

107. A method of inhibiting the growth of a tumor with inflammation in a subject comprising administering an effective amount of the composition of claim 97 or 98 to a subject.

108. A method of inhibiting the growth of a cell having cell surface expression of C10orf54 comprising contacting the cell with an effective amount of the composition of claim 97 or 98.

109. The method of claim 108, wherein the cell is a regulatory T cell.

1 10. The method of claim 108, wherein the cell is a cancerous or pre-cancerous cell.

1 1 1 . A method of modulating an immune response in a subject comprising

administering an effective amount of the composition of claim 97 or 98 to a subject.

1 12. The method of claim 1 1 1 , wherein the modulating comprises:

(a) increasing T cell activation;

(b) increasing T cell proliferation; or

(c) increasing cytokine production.

1 13. A method for detecting C10orf54 in a sample comprising contacting the

sample with the antibody of claim 94 or 95.

1 14. The method of claim 1 13, wherein the sample comprises a cell expressing C10orf54 on its surface.

1 15. A method of treating cancer comprising administering to a subject a

therapeutically effective amount of an anti-C10orf54 antibody or an antibody- drug conjugate comprising an anti-C10orf54 antibody.

1 16. A method of killing a tumor cell comprising contacting a C10orf54-expressing tumor cell with an amount of an anti-C10orf54 antibody or antibody-drug conjugate comprising an anti-C10orf54 antibody effective to kill the tumor cell.

1 17. A kit comprising the antibody of any one of claims 1 to 96.

1 18. A kit comprising the composition of claim 97 or 98.

1 19. An antibody-drug conjugate of the following formulas (la) or (lb):

n (la),

or a pharmaceutically acceptable salt thereof;

wherein:

A is an antibody or antibody fragment according to any one of claims 1 -91 ;

the two depicted cysteine residues are from an opened cysteine-cysteine disulfide bond in A;

each X and X' is independently 0, S, NH, or NR1 wherein R1 is Ch alky!;

Wa is =N- =CH- =CHCH2-, =C(R2)-, or =CHCH(R2)-; Wb -NH-, -N(R1 )-, -CH2- -CH2-NH-, -CH2-N(R1)-, -CH2CH2-, -CH(R2)-, or -CH2CH(R2)-; wherein R1 and R2 are independently C1 -6 alkyl;

CTX is a cytotoxin;

R is any chemical group; or R is absent;

each L1 , L2 and L3 is independently a linker selected from the group consisting of -0- -C(O)-, -S-, -S(O)-, -S(O)2- -NH-, -NCH3-, -(CH2)q- -NH(CH2)2NH-, -OC(O)-, -CO2-, -NHCH2CH2C(0)- -C(0)NHCH2CH2NH-, -NHCH2C(0)-, -NHC(O)-, -C(0)NH- -NCH3C(O)-, -C(O)NCH3- -(CH2CH20)p,

-(CH2CH20)pCH2CH2-, -CH2CH2-(CH2CH20)p- -OCH(CH20-)2, -(AA)r- cyclopentanyl, cyclohexanyl, unsubstituted phenylenyl, and phenylenyl substituted by 1 or 2 substituents selected from the group consisting of halo, CF3-, CF3O-, CH3O-, -C(0)OH, -C(0)OCi-3 alkyl, -C(0)CH3, -CN, -NH-, -NH2, -0-, -OH, -NHCH3, -N(CH3)2, and Ci-3 alkyl;

a, b and c are each independently an integer of 0, 1 , 2 or 3, provided that at least one of a, b or c is 1 ;

each k and k' is independently an integer of 0 or 1 ;

each p is independently an integer of 1 to 14;

each q is independently an integer from 1 to 12;

each AA is independently an amino acid;

each r is 1 to 12;

m is an integer of 1 to 4;

n is an integer of 1 to 4; and

the bond represents a single or a double bond.

120. The antibody-drug conjugate of claim 1 19, wherein A is an anti-C10orf54 antibody.

121 . The antibody-drug conjugate of claim 120, wherein CTX is selected from the group consisting of a tubulin stabilizer, a tubulin destabilizer, a DNA alkylator, a DNA minor groove binder, a DNA intercalator, a topoisomerase I inhibitor, a topoisomerase II inhibitor, a gyrase inhibitor, a protein synthesis inhibitor, a proteosome inhibitor, and an anti-metabolite.

122. The antibody-drug conjugate of claim 1 19, wherein CTX is selected from the group consisting of Actinomycin-D, Amonafide, an auristatin, benzophenone, benzothiazole, a calicheamicin, Camptothecin, CC-1065 (NSC 298223), Cemadotin, Colchicine, Combretastatin A4, Dolastatin, Doxorubicin, Elinafide, Emtansine (DM1 ), Etoposide, KF-12347 (Leinamycin), a maytansinoid, Methotrexate, Mitoxantrone, Nocodazole, Proteosome Inhibitor 1 (PSI 1 ), Roridin A, T-2 Toxin (trichothecene analog), Taxol, a tubulysin, Velcade®, and Vincristine.

123. The antibody-drug conjugate of claim 1 19, wherein CTX is an auristatin, a calicheamicin, a maytansinoid, or a tubulysin.

124. The antibody-drug conjugate of claim 1 19, wherein CTX is

monomethylaunstatin E, monomethylaunstatin F, calicheamicin γ, mertansine, a pyrrolobenzodiazepine, tubulysin T2, tubulysin T3, or tubulysin T4.

125. An antibody-drug conjugate of the following formula (lc):

n (lc);

or a pharmaceutically acceptable salt thereof,

wherein:

A is an anti-C10orf54 antibody;

the two depicted cysteine residues are from an opened cysteine-cysteine disulfide bond in A;

L is a cleavable or a noncleavable linker;

CTX is an auristatin, a pyrrolobenzodiazepine, calicheamicin, doxorubicin, camptothecin, duocarmycin, DM1 , DM4, a maytansinoid, or a tubulysin,

wherein CTX is bonded to L by an amide bond, a carbamate bond, a disulfide bond, an ether bond, a thioether bond, or an ester bond;

the bond represents a single or a double bond; and

n is an integer of 1 to 4.

126. The antibody-drug conjugate of claim 125, wherein L is a noncleavable linker.

127. The antibody-drug conjugate of claim 126, wherein L is

-(CH2)mC(0)- -(CH2CH20)p(CH2CH2)C(0)-, or

-(CH2CH2)(OCH2CH2)pC(0)-;

wherein m is an integer of 5 to 1 1 , and p is an integer of 1 to 3.

128. The antibody-drug conjugate of claim 125, wherein L is a cleavable linker.

129. The antibody-drug conjugate of claim 125, wherein L is

-(CH2)mC(0)-Val-Ala-PAB-0-C(0)-,

-(CH2)mC(0)-Val-Cit-PAB-0-C(0)- -(CH2CH20)p(CH2CH2)C(0)-Val-Ala-PAB-C(0)- -(CH2CH20)p(CH2CH2)C(0)-Val-Cit-PAB-C(0)- -(CH2CH2)(OCH2CH2)pC(0)-Val-Ala-PAB-C(0)-, or

-(CH2CH2)(OCH2CH2)pC(0)-Val-Cit-PAB-C(0)-;

wherein m is an integer of 5 to 1 1 , and p is an integer of 1 to 3.

130. The antibody-drug conjugate of claim 125, wherein n is 4, 3 or 2.

131. The antibody-drug conjugate of claim 125, wherein the opened cysteine- cysteine disulfide bond in A is an interchain disulfide bond.

132. The antibody-drug conjugate of claim 131 , wherein n is 4, 3 or 2.

133. The antibody-drug conjugate of claim 125 or 131 , wherein L is -(CH2)5C(0>

134. The antibody-drug conjugate of claim 125 or 131 , wherein A is a monoclonal antibody, and optionally wherein A comprises two heavy chains and two light chains wherein one or more cysteines in the hinge region of the heavy chains of A have been replaced by another amino acid.

135. The antibody-drug conjugate of claim 134, wherein A is a human lgG1 , lgG2, lgG3 or lgG4.

136. The antibody-drug conjugate of claim 125 or 131 , which is selected from the group consisting of:

451

and

137. A pharmaceutical composition comprising the antibody-drug conjugate or pharmaceutically acceptable salt of claim 125 or 131 , and a pharmaceutically acceptable diluent, carrier or excipient.

138. A method of treating a cancer by administering to a human subject suffering therefrom an effective amount of the antibody-drug conjugate of any one of claims 1 19 to 136, or the pharmaceutical composition of claim 137.

139. An antibo -drug conjugate of the following formula (Id):

wherein:

L is a cleavable or a noncleavable linker;

CTX is an auristatin, a pyrrolobenzodiazepine, calicheamicin, doxorubicin, camptothecin, duocarmycin, DM1 , DM4, a maytansinoid, or a tubulysin, wherein CTX is bonded to L by an amide bond, a carbamate bond, a disulfide bond, an ether bond, a thioether bond, or an ester bond;

Sx is a sulfur atom from a first cysteine residue, and Sy is a sulfur atom from a second cysteine residue, wherein the first cysteine residue and the second cysteine residue are from different chains and/or from the same chain of a multi-chain antibody which is an anti-C10orf54 antibody;

the bond represents a single or a double bond; and

n is an integer of 1 to 4.

140. The antibody-drug conjugate of claim 139, wherein the multi-chain antibody comprises two heavy chains and two light chains.

141. The antibody-drug conjugate of claim 140, wherein the first cysteine residue is from a first heavy chain and the second cysteine residue is from a second heavy chain of the multi-chain antibody.

142. The antibody-drug conjugate of claim 140, wherein the first cysteine residue is from a heavy chain and the second cysteine residue is from a light chain of the multi-chain antibody.

143. The antibody-drug conjugate of claim 140, wherein the first and second

cysteine residues are from the same heavy chain of the multi-chain antibody.

144. The antibody-drug conjugate of claim 139, wherein the multi-chain antibody is a monoclonal antibody, and optionally wherein the multi-chain antibody comprises two heavy chains and two light chains wherein one or more cysteines in the hinge region of the heavy chains of the multi-chain antibody have been replaced by another amino acid.

145. The antibody-drug conjugate of claim 139, wherein the multi-chain antibody is a human lgG1 , lgG2, lgG3 or lgG4.

146. A method of treating a cancer by administering to a human subject suffering therefrom an effective amount of an antibody of any one of claims 1 -92 or an antibody-drug conjugate of any one of claims 139 to 145.

147. The method of claim 138 or 146, wherein the cancer is bladder, breast, colon, connective tissue, rectal, gastric, esophageal, lung, laryx, kidney, oral, ovarian, or prostate cancer, or a sarcoma, melanoma, glioma, lymphoma or leukemia.

148. A method of treating a tumor associated with myeloid-derived suppressor cells (MDSC) comprising administering to a subject an amount of an anti- C10orf54 antibody or an antibody-drug conjugate comprising an anti-C10orf54 antibody.

149. The method of claim 148, wherein the anti-C10orf54 antibody is an antibody of any one of claims 1 -96.

150. The method of claim 148, wherein the antibody drug conjugate comprising then anti-C10orf54 antibody is the antibody drug conjugate of any one of claims 1 19 to 136 and 139 to 145.

51. The method of any of one of claims 148 to 150, wherein the tumor associated with MDSC is colon carcinoma, mammary carcinoma, fibrosarcoma, thymoma, lung carcinoma, renal cell carcinoma, mesothelioma, glioma, lymphoma, sarcoma, prostate carcinoma, sarcoma, or head and neck carcinoma.

52. An isolated antibody that binds to C10orf54, wherein the antibody comprises:

(a) a heavy chain variable (VH) region comprising:

(1) a VH CDR1 having an amino acid sequence selected from the group consisting of SEQ ID NOS: 36, 30, 59-62, 33, 1081, 1086, 1087, 1092, 1099, 1104, 1105, 1110, 1117, 1122, 1123, 1128, and 1291-1335;

(2) a VH CDR2 having an amino acid sequence selected from the group consisting of SEQ ID NOS: 37, 101-104, 50, 114, 99, 100, 31, 65-74, 83-90, 95, 321, 322, 835-842, 34, 847-858, 49, 886-894, 1070-1078, 1082, 1088, 1093, 1098, 1100, 1106, 1111, 1116, 1118, 1124, 1129, and 1336-1384; and

(3) a VH CDR3 having an amino acid sequence selected from the group consisting of SEQ ID NOS: 38, 32, 319, 35, 883-885, 1083, 1089, 1094, 1101, 1107, 1112, 1119, 1125, 1130, and 1385-1424; and/or

(b) a light chain variable (VL) region comprising:

(1) a VL CDR1 having an amino acid sequence selected from the group consisting of SEQ ID NOS: 45, 253-271, 42, 1084, 1090, 1095, 1102, 1108, 1113, 1120, 1126, 1131, and 1425-1472;

(2) a VL CDR2 having an amino acid sequence selected from the group consisting of SEQ ID NOS: 46, 272-275, 40, 843-846, 43, 1045-1048, 1085, 1096, 1103, 1114, 1121, 1132, 1473-1492, and 1526-1528; and

(3) a VL CDR3 having an amino acid sequence selected from the group consisting of SEQ ID NOS: 47, 41 , 44, 1056-1058, 1091 , 1097, 1109, 1115, 1127, 1133, and 1493-1525.

53. An isolated antibody or fragment thereof that binds to C10orf54, wherein the antibody bind to an epitope within aa33-169 of SEQ ID NO: 1079.

154. An isolated antibody or fragment thereof that binds to C10orf54, wherein the antibody bind to an epitope within aa84-169 of SEQ ID NO: 1079.

155. An isolated antibody or fragment thereof that binds to C10orf54, wherein the antibody bind to an epitope within aa1 15-169 of SEQ ID NO: 1079.

156. An isolated antibody or fragment thereof that binds to C10orf54, wherein the antibody bind to an epitope within aa84-1 15 of SEQ ID NO: 1079.

157. An isolated antibody or fragment thereof that binds to C10orf54 comprising a paratope as shown in FIG. 18A-18D.