Anti-PD-L1 antibodies and uses thereof
Provided are anti-PD-L1 antibodies or fragments thereof. The antibodies or fragments thereof specifically bind to the immunoglobulin C domain of the PD-L1 protein. In various example, the antibodies or fragments thereof include a VH CDR1 of SEQ ID NO: 1, a VH CDR2 of SEQ ID NO: 2, a VH CDR3 of SEQ ID NO: 3, a VL CDR1 of SEQ ID NO: 4, a VL CDR2 of SEQ ID NO: 5, and a VL CDR3 of SEQ ID NO: 6, or variants of each thereof. Methods of using the antibodies or fragments thereof for treating and diagnosing diseases such as cancer and infectious diseases are also provided.
1. An antibody or fragment thereof, wherein the antibody or fragment thereof has specificity to a human Programmed death-ligand 1 (PD-L1) protein and comprises a VH CDR1 comprising the amino acid sequence of SEQ ID NO: 1, a VH CDR2 comprising the amino acid sequence of SEQ ID NO: 2, a VH CDR3 comprising the amino acid sequence of SEQ ID NO: 3, a VL CDR1 comprising the amino acid sequence of SEQ ID NO: 4, a VL CDR2 comprising the amino acid sequence of SEQ ID NO: 5, and a VL CDR3 comprising the amino acid sequence of SEQ ID NO: 6.
2. The antibody or fragment thereof of claim 1 , further comprising a heavy chain constant region, a light chain constant region, an Fc region, or the combination thereof.
3. The antibody or fragment thereof of claim 1 , wherein the antibody or fragment thereof is a humanized antibody.
4. An antibody or fragment thereof, wherein the antibody or fragment thereof has specificity to a human Programmed death-ligand 1 (PD-L1) protein and comprises a heavy chain variable region comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 7-26 and a light chain variable region comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 27-33.
5. The antibody or fragment thereof of claim 4 , comprising a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 20 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 28.
6. A composition comprising the antibody or fragment thereof of claim 1 and a pharmaceutically acceptable carrier.
7. An isolated cell comprising one or more polynucleotide encoding the antibody or fragment thereof of claim 1 .
8. An isolated antibody or fragment thereof, wherein the antibody or fragment thereof has specificity to a human PD-L1 protein and comprises:
(a) a VH CDR1 of SEQ ID NO: 1, or a variant of SEQ ID NO: 1 having a single substitution, deletion or insertion at location 1, 2 or 5 of SEQ ID NO: 1;
(b) a VH CDR2 of SEQ ID NO: 2, or a variant of SEQ ID NO: 2 having a single substitution, deletion or insertion at location 7, 8, 14 or 15 of SEQ ID NO: 2;
(c) a VH CDR3 of SEQ ID NO: 3, or a variant of SEQ ID NO: 3 having a single substitution, deletion or insertion at location 1, 2, 3, 4, 5 or 6 of SEQ ID NO: 3;
(d) a VL CDR1 of SEQ ID NO: 4, or a variant of SEQ ID NO: 4 having a single substitution, deletion or insertion at location 3 of SEQ ID NO: 4;
(e) a VL CDR2 of SEQ ID NO: 5, or a variant of SEQ ID NO: 5 having a single substitution, deletion or insertion at location 1, 2, 3, 4, 5 or 6 of SEQ ID NO: 5 and
(f) a VL CDR3 of SEQ ID NO: 6, or a variant of SEQ ID NO: 6 having a single substitution, deletion or insertion at location 11 or 2 of SEQ ID NO: 6.
9. The antibody or fragment thereof of claim 8 , wherein the variant of SEQ ID NO: 1 is selected from the group consisting of SEQ ID NO: 61-67.
10. The antibody or fragment thereof of claim 8 , wherein the variant of SEQ ID NO: 2 is selected from the group consisting of SEQ ID NO: 68-77.
11. The antibody or fragment thereof of claim 8 , wherein the variant of SEQ ID NO: 3 is selected from the group consisting of SEQ ID NO: 78-90.
12. The antibody or fragment thereof of claim 8 , wherein the variant of SEQ ID NO: 4 is selected from the group consisting of SEQ ID NO: 91-92.
13. The antibody or fragment thereof of claim 8 , wherein the variant of SEQ ID NO: 5 is selected from the group consisting of SEQ ID NO: 93-105.
14. The antibody or fragment thereof of claim 8 , wherein the variant of SEQ ID NO: 6 is selected from the group consisting of SEQ ID NO: 106-111.
15. An isolated bispecific antibody comprising a fragment of claim 8 and a second antigen-binding fragment having specificity to a molecular on an immune cell.
16. The bispecific antibody of claim 15 , wherein the molecule is selected from the group consisting of PD-1, CTLA-4, LAG-3, CD28, CD122, 4-1BB, TIM3, OX-40, OX40L, CD40, CD40L, LIGHT, ICOS, ICOSL, GITR, GITRL, TIGIT, CD27, VISTA, B7H3, B7H4, HEVM, BTLA, KIR, and CD47.
17. The bispecific antibody of claim 15 , wherein the fragment and the second fragment each is independently selected from a Fab fragment, a single-chain variable fragment (scFv), or a single-domain antibody.
18. The bispecific antibody of claim 15 , further comprising a Fc fragment.