Anti PD-L1 antibodies
The present disclosure relates to antibodies and antigen-binding fragments thereof that bind to PD-L1, and to methods of using such antibodies and antigen-binding fragments. For example, the present invention provides humanized anti-PD-L1 antibodies and methods of use thereof.
1. An antibody or fragment thereof that binds to PD-L1, wherein the antibody or fragment thereof comprises:
(i) a heavy chain CDR1, CDR2, and CDR3 sequence comprising SEQ ID NO: 87, 88, and 89, respectively, and a light chain CDR1, CDR2, and CDR3 sequence comprising SEQ ID NO: 90, 91, and 92, respectively;
(ii) a heavy chain CDR1, CDR2, and CDR3 sequence comprising SEQ ID NO: 105, 106, and 107, respectively, and a light chain CDR1, CDR2, and CDR3 sequence comprising SEQ ID NO: 108, 109, and 110, respectively;
(iii) a heavy chain CDR1, CDR2, and CDR3 sequence comprising SEQ ID NO: 117, 118, and 119, respectively, and a light chain CDR1, CDR2, and CDR3 sequence comprising SEQ ID NO: 120, 121, and 122, respectively;
(iv) a heavy chain CDR1, CDR2, and CDR3 sequence comprising SEQ ID NO: 129, 130, and 131, respectively, and a light chain CDR1, CDR2, and CDR3 sequence comprising SEQ ID NO: 132, 133, and 134, respectively; or
(v) a heavy chain CDR1, CDR2, and CDR3 sequence comprising SEQ ID NO: 135, 136, and 137, respectively, and a light chain CDR1, CDR2, and CDR3 sequence comprising SEQ ID NO: 138, 139, and 140, respectively.
2. The antibody or fragment thereof of claim 1 , wherein the antibody or fragment thereof is chimeric or humanized.
3. The antibody or fragment thereof of claim 1 , wherein the antibody or fragment thereof is selected from the group consisting of a monoclonal antibody, an scFv, a Fab fragment, an Fab′ fragment, and an F(ab)′ 2 fragment.
4. The antibody or fragment thereof of claim 1 , wherein the antibody or fragment thereof is linked or conjugated to a therapeutic agent.
5. The antibody or fragment thereof of claim 4 , wherein the therapeutic agent is a cytotoxic drug, a radioactive isotope, an immunomodulator, or an antibody.
6. A composition comprising the antibody or fragment thereof of claim 1 .
7. The antibody or fragment of claim 1 , wherein the antibody or fragment thereof comprises a heavy chain CDR1, CDR2, and CDR3 comprising an amino acid sequence according to SEQ ID NOs: 87, 88, and 89, respectively; and a light chain CDR1, CDR2, and CDR3 comprising an amino acid sequence according to SEQ ID NOs: 90, 91, and 92, respectively.
8. The antibody or fragment of claim 1 , wherein the antibody or fragment thereof comprises a heavy chain CDR1, CDR2, and CDR3 comprising an amino acid sequence according to SEQ ID NOs: 105, 106, and 107, respectively; and a light chain CDR1, CDR2, and CDR3 comprising an amino acid sequence according to SEQ ID NOs: 108, 109, and 110, respectively.
9. The antibody or fragment of claim 1 , wherein the antibody or fragment thereof comprises a heavy chain CDR1, CDR2, and CDR3 comprising an amino acid sequence according to SEQ ID NOs: 117, 118, and 119, respectively; and a light chain CDR1, CDR2, and CDR3 comprising an amino acid sequence according to SEQ ID NOs: 120, 121, and 122, respectively.
10. The antibody or fragment of claim 1 , wherein the antibody or fragment thereof comprises a heavy chain CDR1, CDR2, and CDR3 comprising an amino acid sequence according to SEQ ID NOs: 129, 130, and 131, respectively; and a light chain CDR1, CDR2, and CDR3 comprising an amino acid sequence according to SEQ ID NOs: 132, 133, and 134, respectively.
11. The antibody or fragment of claim 1 , wherein the antibody or fragment thereof comprises a heavy chain CDR1, CDR2, and CDR3 comprising an amino acid sequence according to SEQ ID NOs: 135, 136, and 137, respectively; and a light chain CDR1, CDR2, and CDR3 comprising an amino acid sequence according to SEQ ID NOs: 138, 139, and 140, respectively.
12. The antibody or fragment thereof of claim 1 , wherein the antibody or fragment thereof comprises:
(i) a heavy chain variable region comprising SEQ ID NO: 6 and a light chain variable region comprising SEQ ID NO: 8;
(ii) a heavy chain variable region comprising SEQ ID NO: 18 and a light chain variable region comprising SEQ ID NO: 20;
(iii) a heavy chain variable region comprising SEQ ID NO: 26 and a light chain variable region comprising SEQ ID NO: 28;
(iv) a heavy chain variable region comprising SEQ ID NO: 34 and a light chain variable region comprising SEQ ID NO: 36; or
(v) a heavy chain variable region comprising SEQ ID NO: 38 and a light chain variable region comprising SEQ ID NO: 40.
13. The antibody or fragment thereof according to claim 1 , wherein the antibody or fragment thereof has an affinity for PD-L1 of about 10 nM to about 0.01 nM.
14. The antibody or fragment thereof according to claim 13 , wherein the antibody or fragment thereof as an affinity for PD-L1 of about 10 nM or less.
15. The antibody or fragment thereof according to claim 13 , wherein the antibody or fragment thereof as an affinity for PD-L1 of about 1.0 nM or less.
16. The antibody or fragment thereof according to claim 1 , wherein the antibody has a binding EC50 of about 5 ng/mL to about 1000 ng/mL.
17. The antibody or fragment thereof of claim 1 , wherein the antibody blocks binding of PD-L1 to PD-1.
18. The antibody or fragment thereof of claim 17 , wherein the antibody or fragment thereof blocks the binding of PD-L1 to PD-1 at an IC50 of about 5 ng/mL to about 1000 ng/mL.
19. The isolated antibody or fragment thereof of claim 1 , wherein the antibody or fragment increases T cell activation as measured by inflammatory cytokine production.
20. The antibody or fragment thereof according to claim 19 , wherein the antibody or fragment thereof increases T cell production of IL-2 and IFNγ.
21. A composition comprising the antibody or fragment thereof according to claim 1 and a pharmaceutically acceptable carrier.
22. A polynucleotide encoding the antibody or fragment thereof according to claim 1 .
23. An expression vector comprising the isolated polynucleotide according to claim 22 .
24. A host cell comprising the expression vector according to claim 23 .
25. A method for increasing T cell activation, the method comprising contacting T cells with an antibody or fragment thereof according to claim 1 .