Antibodies against TIM3 and uses thereof
Provided herein are antibodies, or antigen-binding portions thereof, that bind to T-cell immunoglobulin and mucin-domain containing-3 (TIM3) protein. Also provided are uses of these antibodies, or antigen-binding portions thereof, in therapeutic applications, such as treatment of cancer. Further provided are cells that produce the antibodies, or antigen-binding portions thereof, polynucleotides encoding the heavy and/or light chain regions of the antibodies, or antigen-binding portions thereof, and vectors comprising the polynucleotides encoding the heavy and/or light chain regions of the antibodies, or antigen-binding portions thereof.
1. An isolated antibody, which binds to human TIM3, comprising two heavy chains and two light chains, wherein each of the heavy chains comprises a heavy chain CDR1 consisting of the amino acid sequence set forth in SEQ ID NO: 41, a heavy chain CDR2 consisting of the amino acid sequence set forth in SEQ ID NO: 122, and a heavy chain CDR3 consisting of the amino acid sequence set forth in SEQ ID NO: 126, and wherein each of the light chains comprises a light chain CDR1 consisting of the amino acid sequence set forth in SEQ ID NO: 64, a light chain CDR2 consisting of the amino acid sequence set forth in SEQ ID NO: 66, and a light chain CDR3 consisting of the amino acid sequence set forth in SEQ ID NO: 68.
2. The isolated antibody of claim 1 , wherein each of the heavy chains comprises a heavy chain variable region (VH) and each of the light chains comprises a light chain variable region (VL), wherein the VH consists of the amino acid sequence set forth in SEQ ID NO: 364 and VL consists of the amino acid sequence set forth in SEQ ID NO: 60.
3. The isolated antibody of claim 1 , wherein each of the heavy chains consists of the amino acid sequence set forth in SEQ ID NO: 349 and each of the light chains consists of the amino acid sequence set forth in SEQ ID NO: 29.
4. The isolated antibody of claim 1 , wherein each of the heavy chains consists of the amino acid sequence set forth in SEQ ID NO: 351 and each of the light chains consists of the amino acid sequence set forth in SEQ ID NO: 29.
5. The isolated antibody of claim 1 , wherein each of the heavy chains consists of the amino acid sequence set forth in SEQ ID NO: 353 and each of the light chains consists of the amino acid sequence set forth in SEQ ID NO: 29.
6. The isolated antibody of claim 1 , wherein each of the heavy chains consists of the amino acid sequence set forth in SEQ ID NO: 350 and each of the light chains consists of the amino acid sequence set forth in SEQ ID NO: 29.
7. The isolated antibody of claim 1 , wherein each of the heavy chains consists of the amino acid sequence set forth in SEQ ID NO: 352 and each of the light chains consists of the amino acid sequence set forth in SEQ ID NO: 29.
8. The isolated antibody of claim 1 , wherein each of the heavy chains consists of the amino acid sequence set forth in SEQ ID NO: 354 and each of the light chains consists of the amino acid sequence set forth in SEQ ID NO: 29.
9. The isolated antibody of claim 1 , wherein the antibody is selected from the group consisting of an IgG1, an IgG2, an IgG3, an IgG4, and a variant thereof.
10. The isolated antibody of claim 1 , comprising an effectorless IgG1 Fc.
11. The isolated antibody of claim 2 , wherein the antibody is selected from the group consisting of an IgG1, an IgG2, an IgG3, an IgG4, and a variant thereof.
12. A composition comprising the antibody of claim 4 , and a carrier.
13. A composition comprising the antibody of claim 7 , and a carrier.
14. The isolated antibody of claim 4 , wherein the antibody comprises at least one disulfide bond linking the two heavy chains together.
15. The isolated antibody of claim 7 , wherein the antibody comprises at least one disulfide bond linking the two heavy chains together.
16. An isolated antibody, which binds to human TIM3, comprising two heavy chains and two light chains, wherein each of the heavy chains comprises the amino acid sequence set forth in SEQ ID NO: 351 and each of the light chains comprises the amino acid sequence set forth in SEQ ID NO: 29.
17. The isolated antibody of claim 16 , wherein each of the heavy chains consists of the amino acid sequence set forth in SEQ ID NO: 351, and each of the light chains consists of the amino acid sequence set forth in SEQ ID NO: 29.
18. The isolated antibody of claim 17 , wherein the antibody comprises at least one disulfide bond linking the two heavy chains together.
19. An isolated antibody, which binds to human TIM3, comprising two heavy chains and two light chains, wherein each of the heavy chains comprises the amino acid sequence set forth in SEQ ID NO: 352 and each of the light chains the amino acid sequence set forth in SEQ ID NO: 29.
20. The isolated antibody of claim 19 , wherein each of the heavy chains consists of the amino acid sequence set forth in SEQ ID NO: 352, and each of the light chains consists of the amino acid sequence set forth in SEQ ID NO: 29.
21. The isolated antibody of claim 20 , wherein the antibody comprises at least one disulfide bond linking the two heavy chains together.
22. A composition comprising the antibody of claim 5 , and a carrier.
23. A composition comprising the antibody of claim 6 , and a carrier.
24. A composition comprising the antibody of claim 17 , and a carrier.
25. A composition comprising the antibody of claim 20 , and a carrier.
26. A composition comprising the antibody of claim 21 , and a carrier.
27. The isolated antibody of claim 5 , wherein the antibody comprises at least one disulfide bond linking the two heavy chains together.
28. The isolated antibody of claim 6 , wherein the antibody comprises at least one disulfide bond linking the two heavy chains together.
29. The isolated antibody of claim 8 , wherein the antibody comprises at least one disulfide bond linking the two heavy chains together.
30. A composition comprising the antibody of claim 8 , and a carrier.