Methods of treatment with CD80 extracellular domain polypeptides
This application relates to use of CD80 (B7-1) extracellular domain (ECD) polypeptides and CD80-ECD fusion molecules and their use in methods of increasing the number of central memory T cells or for treatment for cancer or for use in cancer vaccine compositions.
1. A method of increasing central memory T cell (Tcm) frequency and/or proliferation in a subject, which method comprises administering a CD80 extracellular domain (ECD) fusion molecule to the subject in an amount effective to increase Tcm frequency and/or proliferation, wherein the CD80 ECD fusion molecule comprises a human CD80 ECD polypeptide and a human IgG1 Fc domain.
2. The method of claim 1 , wherein the subject has cancer.
3. The method of claim 2 , wherein the cancer is selected from the group consisting of colorectal cancer, breast cancer, gastric cancer, non-small cell lung cancer, melanoma, squamous cell carcinoma of the head and neck, ovarian cancer, pancreatic cancer, renal cell carcinoma, hepatocellular carcinoma, bladder cancer, and endometrial cancer.
4. The method of claim 2 , wherein the cancer is recurrent or progressive after surgery, chemotherapy, radiation therapy, or a combination thereof.
5. The method of claim 2 , wherein the CD80 ECD fusion molecule is administered in combination with a programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) inhibitor.
6. The method of claim 2 , wherein the CD80 ECD fusion molecule is administered in combination with a cancer vaccine.
7. The method of claim 6 , wherein the CD80 ECD fusion molecule and the cancer vaccine are administered concurrently or sequentially.
8. The method of claim 1 , wherein the central memory T cells are CD95+ and CD28+cells.
9. The method of claim 8 , wherein the central memory T cells are CD4+central memory T cells.
10. The method of claim 8 , wherein the central memory T cells are CD8+ central memory T cells.
11. The method of claim 1 , wherein increased central memory T cell proliferation is detected in a sample obtained from the subject at least 7 days after administration of the CD80 ECD fusion molecule.
12. The method of claim 11 , wherein the central memory T cell proliferation is determined by measuring Ki67 expression.
13. The method of claim 11 , wherein the sample is a plasma sample, blood sample, or tumor sample.
14. The method of claim 1 , wherein the human CD80 ECD polypeptide comprises the amino acid sequence of SEQ ID NO:5.
15. The method of claim 1 , wherein the human IgG1 Fc domain comprises the amino acid sequence of SEQ ID NO:14.
16. The method of claim 1 , wherein the CD80 ECD fusion molecule comprises the amino acid sequence of SEQ ID NO:20.
17. The method of claim 1 , wherein the CD80 ECD fusion molecule comprises 10-60 molecules of sialic acid (SA).
18. The method of claim 1 , wherein Tcm frequency and/or proliferation is increased relative to Tem frequency and/or proliferation in the subject prior to said administering.
19. The method of claim 1 , wherein the central memory T cells are CD4+central memory T cells.
20. The method of claim 1 , wherein the central memory T cells are CD8+central memory T cells.