Anti-PD-L1 antibodies and diagnostic uses thereof
The invention provides programmed death-ligand 1 (PD-L1) antibodies and methods of using the same.
1. An isolated antibody that specifically binds PD-L1, wherein the antibody comprises a heavy chain variable domain (VH) and a light chain variable domain (VL) that comprises the following hypervariable regions (HVRs):
(a) an HVR-H1 comprising the amino acid sequence of SNGLT (SEQ ID NO: 2);
(b) an HVR-H2 comprising the amino acid sequence of TINKDASAYYASWAKG (SEQ ID NO: 3);
(c) an HVR-H3 comprising the amino acid sequence of IAFKTGTSI (SEQ ID NO:4);
(d) an HVR-L1 comprising the amino acid sequence of QASESVYSNNYLS (SEQ ID NO: 9);
(e) an HVR-L2 comprising the amino acid sequence of LASTLAS (SEQ ID NO: 10); and
(f) an HVR-L3 comprising the amino acid sequence of IGGKSSSTDGNA (SEQ ID NO: 11).
2. The antibody of claim 1 , wherein the antibody further comprises the following heavy chain variable domain framework regions (FRs):
(a) FR-H1 comprising the amino acid sequence of QSLEESGGRLVKPDETLTITCTVSGIDLS (SEQ ID NO:5);
(b) FR-H2 comprising the amino acid sequence of WVRQAPGEGLEWIG (SEQ ID NO: 6);
(c) FR-H3 comprising the amino acid sequence of RLTISKPSSTKVDLKITSPTTEDTATYFCGR (SEQ ID NO: 7); and
(d) FR-H4 comprising the amino acid sequence of WGPGTLVTVSS (SEQ ID NO: 8).
3. The antibody of claim 1 , wherein the anti bodyfurther comprises the following light chain variable domain framework regions (FRs) FRs:
(a) FR-L1 comprising the amino acid sequence of AIVMTQTPSPVSAAVGGTVTINC (SEQ ID NO: 12);
(b) FR-L2 comprising the amino acid sequence of WFQQKPGQPPKLLIY (SEQ ID NO: 13);
(c) FR-L3 comprising the amino acid sequence of GVPSRFKGSGSGTQFTLTISGVQCDDAATYYC (SEQ ID NO: 14); and
(d) FR-L4 comprising the amino acid sequence of FGGGTEVVVR (SEQ ID NO: 15).
4. The antibody of claim 1 , wherein the antibody comprises a VH sequence of SEQ ID NO: 16 and a VL sequence of SEQ ID NO: 17.
5. The antibody of claim 1 , wherein the antibody is a monoclonal antibody.
6. The antibody of claim 1 , wherein the antibody is an IgG antibody.
7. The antibody of claim 1 , wherein the antibody is an anti body fragment that specifically binds PD-L1.
8. The antibody of claim 7 , wherein the antibody fragment is selected from the group consisting of Fab, single chain variable fragment (scFv), Fv, Fab′, Fab′-SH, F(ab′) 2 , and diabody.
9. An immunoconjugate comprising the antibody of claim 1 .
10. An isolated nucleic acid encoding an isolated antibody of claim 1 .
11. A vector comprising the nucleic acid of claim 10 .
12. A host cell comprising the vector of claim 11 .
13. A method of detecting the presence or expression level of PD-L1 in a biological sample from a subject comprising contacting the biological sample with the antibody of claim 1 and detecting the presence of the bound antibody.
14. The method of claim 13 , wherein the subject is a human.
15. The method of claim 13 , wherein the detecting is by immunohistochemistry (IHC), immunofluorescence (IF), flow cytometry, enzyme-linked immunosorbent assay (ELISA) LISA, or immunoblotting.
16. The method of claim 13 , wherein the sample comprises a fixed tissue.
17. The method of claim 13 , wherein the sample is from a subject having, or at risk of, a cancer.
18. The method of claim 17 , wherein the cancer is selected from the group consisting of non-small cell lung cancer, squamous cell cancer, small-cell lung cancer, cancer of the peritoneum, hepatocellular cancer, gastrointestinal cancer, pancreatic cancer, glioma, cervical cancer, ovarian cancer, liver cancer, bladder cancer, hepatoma, breast cancer, colon cancer, colorectal cancer, endometrial or uterine carcinoma, salivary gland carcinoma, kidney cancer, liver cancer, prostate cancer, vulval cancer, thyroid cancer, hepatic carcinoma, leukemia, and head and neck cancer.
19. The method of claim 18 , wherein the cancer is non-small cell lung cancer (NSCLC).
20. The method of claim 17 , wherein the sample is a tumor sample.
21. The method of claim 20 , wherein the tumor sample comprises tumor infiltrating immune cells, tumor cells, stromal cells, or any combination thereof.
22. The method of claim 21 , wherein the tumor sample has a detectable expression level of PD-L1 in tumor-infiltrating immune cells that comprise about 1% or more of the tumor sample by area.
23. The method of claim 21 , wherein the tumor sample has a detectable expression level of PD-L1 in tumor-infiltrating immune cells that comprise about 5% or more of the tumor sample by area.
24. The method of claim 21 , wherein the tumor sample has a detectable expression level of PD-L1 in tumor-infiltrating immune cells that comprise about 10% or more of the tumor sample by area.
25. The method of claim 21 , wherein the tumor sample has a detectable expression level of PD-L1 in about 1% or more of the tumor cells in the tumor sample.
26. The method of claim 21 , wherein the tumor sample has a detectable expression level of PD-L1 in about 5% or more of the tumor cells in the tumor sample.
27. The method of claim 21 , wherein the tumor sample has a detectable expression level of PD-L1 in about 10% or more of the tumor cells in the tumor sample.
28. The method of claim 21 , wherein the tumor sample has a detectable expression level of PD-L1 in about 50% or more of the tumor cells in the tumor sample.