【Technical Field】
Cross-Reference to Related Applications
This application claims the benefits of KR 10-2020-0094053 filed on July 28,
2020 with the Korean Intellectual Property Office, the entire disclosure of which is
herein incorporated by reference.
10 The disclosure relates to an anti-LILRB1 antibody and uses thereof. More
specifically, an anti-LILRB1 antibody or antigen-binding fragment thereof, and a use
thereof for cancer therapy are provided.
【Background Art】
15 Leukocyte immunoglobulin-like receptor subfamily B member 1 (LILRB1; also
known as ILT2, CD85j, or LIR-1) is an inhibitory receptor, which is expressed in cells
such as B cells, T cells, NK cells, dendritic cells, macrophages, and other immune
cells. LILRB1 participates in a signal transduction mechanism of inhibiting activities of
immune cells by binding classical and non-classical MHC class I.
20 Therefore, it is required to develop a substance targeting LILRB1.
【Disclosure】
【Technical Problem】
An embodiment provides an anti-LILRB1 antibody, which binds to LILRB1, or
25 antigen-binding fragment thereof. The anti-LILRB1 antibody or antigen-binding
fragment thereof may have an activity to inhibit immune evasion of cancer cells.
Furthermore, the anti-LILRB1 antibody or antigen-binding fragment thereof may have
an anti-cancer effect. The anti-cancer effect may be against a cancer cell expressing
or overexpressing MHC Class I on the surface.
30 Another embodiment provides a pharmaceutical composition for treatment
and/or prevention of a cancer, the composition comprising the anti-LILRB1 antibody
3
or antigen-binding fragment thereof as an active ingredient. Another embodiment
provides a method for treating and/or preventing cancer, comprising administering to
a subject in need thereof a pharmaceutically effective amount of the anti-LILRB1
antibody or antigen-binding fragment thereof. Another embodiment provides a use of
5 the anti-LILRB1 antibody or antigen-binding fragment thereof for the treatment and/or
prevention of cancer or for the manufacture of a pharmaceutical composition for the
treatment and/or prevention of cancer.
Another embodiment provides a pharmaceutical composition for inhibiting
immune evasion of cancer cells comprising the anti-LILRB1 antibody or antigen10 binding fragment thereof. Another embodiment provides a method for inhibiting
immune evasion of cancer cells, comprising administering a pharmaceutically
effective amount of the anti-LILRB1 antibody or antigen-binding fragment thereof to a
subject in need of inhibiting immune evasion of cancer cells. Another example
provides a use of the anti-LILRB1 antibody or antigen-binding fragment thereof for
15 inhibiting immune evasion of cancer cells, or for the manufacture of a pharmaceutical
composition for inhibiting immune evasion of cancer cells.
【Technical Solution】
An embodiment provides an anti-LILRB1 antibody, which binds to LILRB1, or
20 antigen-binding fragment thereof. The anti-LILRB1 antibody or antigen-binding
fragment thereof may have an activity to inhibit immune evasion of cancer cells. In
addition, the anti-LILRB1 antibody or antigen-binding fragment thereof may have an
anti-cancer effect.
The anti-LILRB1 antibody or antigen-binding fragment thereof may comprise the
25 following complementarity determining regions (CDRs):
Based on the CDR definition according to Kabat numbering (Kabat, E.A., Wu,
T.T., Perry, H., Gottesman, K. and Foeller, C. (1991) Sequences of Proteins of
Immunological Interest, Fifth Edition. NIH Publication No. 91-3242;
http://www.abysis.org/),
30 a CDR-L1 comprising an amino acid sequence of SEQ ID NO: 1, 13, 25, 37,
49, 61, 73, 85, 97, 109, 121, 133, 145, 157, 169, 181, 193, 205, or 217,
4
a CDR-L2 comprising an amino acid sequence of SEQ ID NO: 2, 14, 26, 38,
50, 62, 74, 86, 98, 110, 122, 134, 146, 158, 170, 182, 194, 206, or 218,
a CDR-L3 comprising an amino acid sequence of SEQ ID NO: 3, 15, 27, 39,
51, 63, 75, 87, 99, 111, 123, 135, 147, 159, 171, 183, 195, 207, or 219,
5 a CDR-H1 comprising an amino acid sequence of SEQ ID NO: 4, 16, 28, 40,
52, 64, 76, 88, 100, 112, 124, 136, 148, 160, 172, 184, 196, 208 or 220,
a CDR-H2 comprising an amino acid sequence of SEQ ID NO: 5, 17, 29, 41,
53, 65, 77, 89, 101, 113, 125, 137, 149, 161, 173, 185, 197, 209 or 221, and
a CDR-H3 comprising an amino acid sequence of SEQ ID NO: 6, 18, 30, 42,
10 54, 66, 78, 90, 102, 114, 126, 138, 150, 162, 174, 186, 198, 210 or 222.

【CLAIMS】
【Claim 1】
An anti-LILRB1 antibody or antigen-binding fragment thereof, comprising
complementarity determining regions (CDRs) as follows:
5 a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 1, 13, 25, 37,
49, 61, 73, 85, 97, 109, 121, 133, 145, 157, 169, 181, 193, 205 or 217,
a CDR-L2 comprising the amino acid sequence of SEQ ID NO: 2, 14, 26, 38,
50, 62, 74, 86, 98, 110, 122, 134, 146, 158, 170, 182, 194, 206, or 218,
a CDR-L3 comprising the amino acid sequence of SEQ ID NO: 3, 15, 27, 39,
10 51, 63, 75, 87, 99, 111, 123, 135, 147, 159, 171, 183, 195, 207, or 219,
a CDR-H1 comprising the amino acid sequence of SEQ ID NO: 4, 16, 28, 40,
52, 64, 76, 88, 100, 112, 124, 136, 148, 160, 172, 184, 196, 208, or 220,
a CDR-H2 comprising the amino acid sequence of SEQ ID NO: 5, 17, 29, 41,
53, 65, 77, 89, 101, 113, 125, 137, 149, 161, 173, 185, 197, 209, or 221, and
15 a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 6, 18, 30, 42,
54, 66, 78, 90, 102, 114, 126, 138, 150, 162, 174, 186, 198, 210, or 222,
wherein the CDRs are defined based on Kabat numbering.
【Claim 2】
The anti-LILRB1 antibody or antigen-binding fragment thereof of claim 1,
20 comprising:
(1) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 1, a CDRL2 comprising the amino acid sequence of SEQ ID NO: 2, a CDR-L3 comprising the
amino acid sequence of SEQ ID NO: 3, a CDR-H1 comprising the amino acid
sequence of SEQ ID NO: 4, a CDR-H2 comprising the amino acid sequence of SEQ
25 ID NO: 5, and a CDR-H3 comprising the amino acid sequence of SEQ ID NO: 6;
(2) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 13, a
CDR-L2 comprising the amino acid sequence of SEQ ID NO: 14, a CDR-L3
comprising the amino acid sequence of SEQ ID NO: 15, a CDR-H1 comprising the
amino acid sequence of SEQ ID NO: 16, a CDR-H2 comprising the amino acid
30 sequence of SEQ ID NO: 17, and a CDR-H3 comprising the amino acid sequence of
SEQ ID NO: 18;
55
(3) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 25, a
CDR-L2 comprising the amino acid sequence of SEQ ID NO: 26, a CDR-L3
comprising the amino acid sequence of SEQ ID NO: 27, a CDR-H1 comprising the
amino acid sequence of SEQ ID NO: 28, a CDR-H2 comprising the amino acid
5 sequence of SEQ ID NO: 29, and a CDR-H3 comprising the amino acid sequence of
SEQ ID NO: 30;
(4) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 37, a
CDR-L2 comprising the amino acid sequence of SEQ ID NO: 38, a CDR-L3
comprising the amino acid sequence of SEQ ID NO: 39, a CDR-H1 comprising the
10 amino acid sequence of SEQ ID NO: 40, a CDR-H2 comprising the amino acid
sequence of SEQ ID NO: 41, and a CDR-H3 comprising the amino acid sequence of
SEQ ID NO: 42;
(5) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 49, a
CDR-L2 comprising the amino acid sequence of SEQ ID NO: 50, a CDR-L3
15 comprising the amino acid sequence of SEQ ID NO: 51, a CDR-H1 comprising the
amino acid sequence of SEQ ID NO: 52, a CDR-H2 comprising the amino acid
sequence of SEQ ID NO: 53, and a CDR-H3 comprising the amino acid sequence of
SEQ ID NO: 54;
(6) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 61, a
20 CDR-L2 comprising the amino acid sequence of SEQ ID NO: 62, a CDR-L3
comprising the amino acid sequence of SEQ ID NO: 63, a CDR-H1 comprising the
amino acid sequence of SEQ ID NO: 64, a CDR-H2 comprising the amino acid
sequence of SEQ ID NO: 65, and a CDR-H3 comprising the amino acid sequence of
SEQ ID NO: 66;
25 (7) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 73, a
CDR-L2 comprising the amino acid sequence of SEQ ID NO: 74, a CDR-L3
comprising the amino acid sequence of SEQ ID NO: 75, a CDR-H1 comprising the
amino acid sequence of SEQ ID NO: 76, a CDR-H2 comprising the amino acid
sequence of SEQ ID NO: 77, and a CDR-H3 comprising the amino acid sequence of
30 SEQ ID NO: 78;
(8) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 85, a
56
CDR-L2 comprising the amino acid sequence of SEQ ID NO: 86, a CDR-L3
comprising the amino acid sequence of SEQ ID NO: 87, a CDR-H1 comprising the
amino acid sequence of SEQ ID NO: 88, a CDR-H2 comprising the amino acid
sequence of SEQ ID NO: 89, and a CDR-H3 comprising the amino acid sequence of
5 SEQ ID NO: 90;
(9) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 97, a
CDR-L2 comprising the amino acid sequence of SEQ ID NO: 98, a CDR-L3
comprising the amino acid sequence of SEQ ID NO: 99, a CDR-H1 comprising the
amino acid sequence of SEQ ID NO: 100, a CDR-H2 comprising the amino acid
10 sequence of SEQ ID NO: 101, and a CDR-H3 comprising the amino acid sequence
of SEQ ID NO: 102;
(10) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 109, a
CDR-L2 comprising the amino acid sequence of SEQ ID NO: 110, a CDR-L3
comprising the amino acid sequence of SEQ ID NO: 111, a CDR-H1 comprising the
15 amino acid sequence of SEQ ID NO: 112, a CDR-H2 comprising the amino acid
sequence of SEQ ID NO: 113, and a CDR-H3 comprising the amino acid sequence of
SEQ ID NO: 114;
(11) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 121, a
CDR-L2 comprising the amino acid sequence of SEQ ID NO: 122, a CDR-L3
20 comprising the amino acid sequence of SEQ ID NO: 123, a CDR-H1 comprising the
amino acid sequence of SEQ ID NO: 124, a CDR-H2 comprising the amino acid
sequence of SEQ ID NO: 125, and a CDR-H3 comprising the amino acid sequence
of SEQ ID NO: 126;
(12) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 133, a
25 CDR-L2 comprising the amino acid sequence of SEQ ID NO: 134, a CDR-L3
comprising the amino acid sequence of SEQ ID NO: 135, a CDR-H1 comprising the
amino acid sequence of SEQ ID NO: 136, a CDR-H2 comprising the amino acid
sequence of SEQ ID NO: 137, and a CDR-H3 comprising the amino acid sequence
of SEQ ID NO: 138;
30 (13) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 145, a
CDR-L2 comprising the amino acid sequence of SEQ ID NO: 146, a CDR-L3
57
comprising the amino acid sequence of SEQ ID NO: 147, a CDR-H1 comprising the
amino acid sequence of SEQ ID NO: 148, a CDR-H2 comprising the amino acid
sequence of SEQ ID NO: 149, and a CDR-H3 comprising the amino acid sequence
of SEQ ID NO: 150;
5 (14) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 157, a
CDR-L2 comprising the amino acid sequence of SEQ ID NO: 158, a CDR-L3
comprising the amino acid sequence of SEQ ID NO: 159, a CDR-H1 comprising the
amino acid sequence of SEQ ID NO: 160, a CDR-H2 comprising the amino acid
sequence of SEQ ID NO: 161, and a CDR-H3 comprising the amino acid sequence
10 of SEQ ID NO: 162;
(15) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 169, a
CDR-L2 comprising the amino acid sequence of SEQ ID NO: 170, a CDR-L3
comprising the amino acid sequence of SEQ ID NO: 171, a CDR-H1 comprising the
amino acid sequence of SEQ ID NO: 172, a CDR-H2 comprising the amino acid
15 sequence of SEQ ID NO: 173, and a CDR-H3 comprising the amino acid sequence
of SEQ ID NO: 174;
(16) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 181, a
CDR-L2 comprising the amino acid sequence of SEQ ID NO: 182, a CDR-L3
comprising the amino acid sequence of SEQ ID NO: 183, a CDR-H1 comprising the
20 amino acid sequence of SEQ ID NO: 184, a CDR-H2 comprising the amino acid
sequence of SEQ ID NO: 185, and a CDR-H3 comprising the amino acid sequence
of SEQ ID NO: 186;
(17) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 193, a
CDR-L2 comprising the amino acid sequence of SEQ ID NO: 194, a CDR-L3
25 comprising the amino acid sequence of SEQ ID NO: 195, a CDR-H1 comprising the
amino acid sequence of SEQ ID NO: 196, a CDR-H2 comprising the amino acid
sequence of SEQ ID NO: 197, and a CDR-H3 comprising the amino acid sequence
of SEQ ID NO: 198;
(18) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 205, a
30 CDR-L2 comprising the amino acid sequence of SEQ ID NO: 206, a CDR-L3
comprising the amino acid sequence of SEQ ID NO: 207, a CDR-H1 comprising the
58
amino acid sequence of SEQ ID NO: 208, a CDR-H2 comprising the amino acid
sequence of SEQ ID NO: 209, and a CDR-H3 comprising the amino acid sequence
of SEQ ID NO: 210; or
(19) a CDR-L1 comprising the amino acid sequence of SEQ ID NO: 217, a
5 CDR-L2 comprising the amino acid sequence of SEQ ID NO: 218, a CDR-L3
comprising the amino acid sequence of SEQ ID NO: 219, a CDR-H1 comprising the
amino acid sequence of SEQ ID NO: 220, a CDR-H2 comprising the amino acid
sequence of SEQ ID NO: 221, and a CDR-H3 comprising the amino acid sequence
of SEQ ID NO: 222.
10 【Claim 3】
The anti-LILRB1 antibody or antigen-binding fragment thereof of claim 1,
comprising:
a light chain variable region comprising the amino acid sequence of SEQ ID
NO: 7, 19, 31, 43, 55, 67, 79, 91, 103, 115, 127, 139, 151, 163, 175, 187, 199, 211,
15 or 223, and
a heavy chain variable region comprising the amino acid sequence of SEQ ID
NO: 9, 21, 33, 45, 57, 69, 81, 93, 105, 117, 129, 141, 153, 165, 177, 189, 201, 213,
or 225.
【Claim 4】
20 The anti-LILRB1 antibody or antigen-binding fragment thereof of claim 1,
wherein the antibody is a human IgG1 or IgG4 antibody.
【Claim 5】
The anti-LILRB1 antibody or antigen-binding fragment thereof of claim 1,
wherein the antigen-binding fragment is scFv, (scFv)2, Fab, Fab', F(ab')2 of the anti25 LILRB1 antibody, a fusion polypeptide comprising scFv fused with an
immunoglobulin Fc, or a fusion polypeptide comprising scFv fused with a constant
region of a light chain.
【Claim 6】
A pharmaceutical composition for treating or preventing a cancer, comprising
30 the anti-LILRB1 antibody or antigen-binding fragment thereof of any one of claims 1
59
to 5.
【Claim 7】
The pharmaceutical composition of claim 6, wherein the cancer is
characterized by overexpression of MHC Class I.
5 【Claim 8】
The pharmaceutical composition of claim 6, wherein the composition has an
activity to inhibit immune evasion of cancer cells.
【Claim 9】
A nucleic acid molecule encoding the antibody or antigen-binding fragment
10 thereof of any one of claims 1 to 5.
【Claim 10】
A recombinant vector comprising the nucleic acid molecule of claim 9.
【Claim 11】
A recombinant cell comprising the nucleic acid molecule of claim 9 or a
15 recombinant vector comprising the nucleic acid molecule.
【Claim 12】
A method of preparing an anti-LILRB1 antibody or antigen-binding fragment
thereof, comprising culturing the recombinant cell of claim 11.
【Claim 13】
20 A pharmaceutical composition for inhibiting immune evasion of cancer cells,
comprising the anti-LILRB1 antibody or antigen-binding fragment thereof of any one
of claims 1 to 5.