Anti-KLRG1 antibodies
The invention relates to antibodies, or antigen-binding fragments thereof, that specifically binds to killer cell lectin-like receptor G1 (KLRG1). Such antibodies, or antigen-binding fragments thereof, are useful for various therapeutic or diagnostic purposes including treatment of cancers and to increase the effectiveness of vaccines.
1. An antibody, or antigen binding fragment thereof, comprising:
(a) a heavy chain variable (VH) domain comprising complementarity-determining regions (CDRs) of CDR-H1, CDR-H2, and CDR-H3 consisting of the amino acid sequences of SEQ ID NOs: 13, 14, and 15, respectively; and
(b) a light chain variable (VL) domain comprising a CDR-L2 and CDR-L3 consisting of the amino acid sequences of SEQ ID NO: 17 and SEQ ID NO: 18, respectively and a CDR-L1 consisting of the amino acid sequence of SEQ ID NO: 16 or the amino acid sequence of SEQ ID NO: 16 wherein NG is substituted with NA, QG, or KG;
wherein said antibody, or antigen binding fragment thereof, specifically binds to the extracellular domain of human killer cell lectin-like receptor subfamily G member 1 (KLRG1) and the extracellular domain of cynomolgus monkey KLRG1.
2. The antibody, or antigen binding fragment thereof, of claim 1 , wherein CDR-L1 (SEQ ID NO: 16) has NG substituted with NA.
3. The antibody, or antigen binding fragment thereof, of claim 1 , comprising:
(i) the VH domain sequence of SEQ ID NO: 3 and the VL domain sequence of SEQ ID NO: 4, or the VL domain sequence of SEQ ID NO:4, wherein NG is substituted with NA in the CDR-L1; or
(ii) the VH domain sequence of SEQ ID NO: 27 and the VL domain sequence of SEQ ID NO: 28, or the VL domain sequence of SEQ ID NO:28, wherein NG is substituted with NA in the CDR-L1.
4. The antibody, or antigen binding fragment thereof of claim 1 , wherein the antibody specifically binds to an amino acid sequence that is at least one amino acid sequence selected from group consisting of SEQ ID NO: 89 and SEQ ID NO: 90.
5. The antibody, or antigen binding fragment thereof, of claim 1 , wherein the antibody specifically binds to the extracellular domain of KLRG1 with an affinity, as expressed in K D , of at least 2 nM, 1 nM, 100 pM, 10 pM, or 5 pM.
6. The antibody, or antigen binding fragment thereof of claim 1 , wherein the antibody is humanized.
7. The antibody, or antigen binding fragment thereof of claim 1 , wherein the antibody is IgG1 or IgG4.
8. A pharmaceutical composition comprising the antibody or antigen binding fragment thereof of claim 1 and a pharmaceutically acceptable carrier.
9. An antibody, or antigen binding fragment thereof, comprising:
(a) a heavy chain variable (VH) domain comprising complementarity-determining regions (CDRs) of CDR-H1, CDR-H2, and CDR-H3 consisting of the amino acid sequences of SEQ ID NOs: 7, 8, and 9, respectively; and
(b) a light chain variable (VL) domain comprising a CDR-L2 and CDR-L3 consisting of the amino acid sequences of SEQ ID NO: 11 and SEQ ID NO: 12, respectively and a CDR-L1 consisting of the amino acid sequence of SEQ ID NO: 10 or the amino acid sequence of SEQ ID NO: 10 wherein NG is substituted with NA, QG, or KG;
wherein said antibody, or antigen binding fragment thereof, specifically binds to the extracellular domain of human killer cell lectin-like receptor subfamily G member 1 (KLRG1) and the extracellular domain of cynomolgus monkey KLRG1.
10. The antibody, or antigen binding fragment thereof, of claim 9 , wherein CDR-L1 (SEQ ID NO: 10) has NG substituted with NA.
11. The antibody, or antigen binding fragment thereof, of claim 9 , comprising:
(i) the VH domain sequence of SEQ ID NO: 1 and the VL domain sequence of SEQ ID NO: 2, or the VL domain sequence of SEQ ID NO: 2, wherein NG is substituted with NA in the CDR-L1; or
(ii) the VH domain sequence of SEQ ID NO: 25 and the VL domain sequence of SEQ ID NO: 26, or the VL domain sequence of SEQ ID NO: 26, wherein NG is substituted with NA in the CDR-L1.
12. The antibody, or antigen binding fragment thereof of claim 9 , wherein the antibody specifically binds to an amino acid sequence that is at least one amino acid sequence selected from group consisting of SEQ ID NO: 89 and SEQ ID NO: 90.
13. The antibody, or antigen binding fragment thereof of claim 9 , wherein the antibody specifically binds to the extracellular domain of KLRG1 with an affinity, as expressed in K D , of at least 2 nM, 1 nM, 100 pM, 10 pM, or 5 pM.
14. The antibody, or antigen binding fragment thereof of claim 9 , wherein the antibody is humanized.
15. The antibody, or antigen binding fragment thereof of claim 9 , wherein the antibody is IgG1 or IgG4.
16. A pharmaceutical composition comprising the antibody or antigen binding fragment thereof of claim 9 and a pharmaceutically acceptable carrier.