Programmed death 1 ligand 1 (PD-L1) binding proteins and methods of use thereof
The present disclosure provides proteins, such as antibodies, that include an antigen binding portion that specifically binds to Programmed Death 1 Ligand 1 (PD-L1). Also provided are nucleic acids encoding the proteins, and cells (e.g., genetically modified cytotoxic lymphocytes) that include such nucleic acids. In some embodiments, a subject method includes reducing the interaction between PD-L1 on a first-cell and PD-1 on a second cell. In some cases, the contacting is in vivo. For example, the methods and compositions provided can be used in the treatment of viral infection and cancer, such as the treatment of solid tumors via ACT or via administration of a subject protein that specifically binds to PD-L1.
1. A genetically engineered cell, wherein the cell expresses a protein that specifically binds to PD-L1; wherein the protein comprises an antigen binding portion comprising:
(a) a first polypeptide comprising the 3 CDR amino acid sequences set forth in SEQ ID NOs:2-4, and a second polypeptide comprising the 3 CDR amino acid sequences set forth in SEQ ID NOs:6-8; or
(b) a first polypeptide comprising the 3 CDR amino acid sequences set forth in SEQ ID NOs: 10-12, and a second polypeptide comprising the 3 CDR amino acid sequences set forth in SEQ ID NOs:14-16.
2. The genetically engineered cell of claim 1 , wherein the cell is a cytotoxic lymphocyte.
3. The genetically engineered cell of claim 2 , wherein the cytotoxic lymphocyte is a T-cell.
4. The genetically engineered cell of claim 2 , wherein the cytotoxic lymphocyte is a CD4+T-helper cell.
5. The genetically engineered cell of claim 2 , wherein the cytotoxic lymphocyte is a natural killer (NK) cell.
6. The genetically engineered cell of claim 2 , wherein the cytotoxic lymphocyte is a tumor infiltrating lymphocyte (TIL) derived from a tumor from a subject.
7. The genetically engineered cell of claim 2 , wherein the genetically modified cytotoxic lymphocyte comprises a receptor specific for an antigen from a tumor.
8. The genetically engineered cell of claim 1 , wherein the cell expresses and secretes the protein.
9. The genetically engineered cell of claim 1 , wherein the genetically modified cell constitutively expresses the protein that specifically binds to PD-L1.
10. The genetically engineered cell of claim 1 , wherein the antigen binding portion comprises a first polypeptide comprising the 3 CDR amino acid sequences set forth in SEQ ID NOs:2-4, and a second polypeptide comprising the 3 CDR amino acid sequences set forth in SEQ ID NOs:6-8.
11. The genetically engineered cell of claim 1 , wherein the first polypeptide comprises the amino acid sequence set forth in SEQ ID NO:1, and the second polypeptide comprises the amino acid sequence set forth in SEQ ID NO:5.
12. The genetically engineered cell of claim 1 , wherein the antigen binding portion comprises a first polypeptide comprising the 3 CDR amino acid sequences set forth in SEQ ID NOs:10-12, and a second polypeptide comprising the 3 CDR amino acid sequences set forth in SEQ ID NOs:14-16.
13. The genetically engineered cell of claim 1 , wherein the first polypeptide comprises the amino acid sequence set forth in SEQ ID NO:9, and the second polypeptide comprises the amino acid sequence set forth in SEQ ID NO:13.
14. The genetically engineered cell of claim 1 , wherein the first polypeptide is a light chain, and the second polypeptide is a heavy chain.
15. The genetically engineered cell of claim 1 , wherein the protein is a single-chain antibody (scFv) and the first and second polypeptides are fused directly or via a linker to one another.
16. The genetically engineered cell of claim 15 , wherein the scFv comprises the amino acid sequence set forth in SEQ ID NO:17 or SEQ ID NO:19.
17. The genetically engineered cell of claim 1 , wherein the protein is a maxibody comprising an immunoglobulin Fc domain fused directly or via a linker to the antigen binding portion.
18. The genetically engineered cell of claim 17 , wherein the immunoglobulin Fc domain is an IgG1 Fc domain or an IgG4 Fc domain.
19. The genetically engineered cell of claim 1 , wherein the protein comprises the amino acid sequence set forth in SEQ ID NO:18 or SEQ ID NO:20.
20. The genetically engineered cell of claim 1 , wherein the protein is a humanized antibody.
21. The genetically engineered cell of claim 1 , comprising a nucleic acid comprising a nucleotide sequence encoding the protein that specifically binds to PD-L1.
22. The genetically engineered cell of claim 1 , wherein the nucleic acid is integrated into the cell's genome.