CD80 variant immunomodulatory proteins and uses thereof
Provided herein are variant CD80 polypeptides, immunomodulatory proteins comprising variant CD80 polypeptides, and nucleic acids encoding such proteins. The immunomodulatory proteins provide therapeutic utility for a variety of immunological and oncological conditions. Compositions and methods for making and using such proteins are provided.
1. An engineered immune cell, comprising a nucleic acid encoding an immunomodulatory protein comprising a variant CD80 polypeptide, wherein the variant CD80 polypeptide comprises the amino acid substitutions H18Y, A26E, E35D, M47L, V68M, A71G and D90G in the amino acid sequence set forth in SEQ ID NO: 2 or a portion thereof comprising the IgV domain, wherein the IgV domain is amino acids 35-141 of SEQ ID NO:1.
2. The engineered immune cell of claim 1 , wherein the immunomodulatory protein is secretable from the engineered cell.
3. The engineered immune cell of claim 1 , wherein the variant CD80 polypeptide comprises the sequence set forth in SEQ ID NO: 2276.
4. The engineered immune cell of claim 2 , wherein the variant CD80 polypeptide comprises the sequence set forth in SEQ ID NO: 2276.
5. The engineered immune cell of claim 1 , wherein the immune cell is an antigen presenting cell (APC).
6. The engineered immune cell of claim 2 , wherein the immune cell is an antigen presenting cell (APC).
7. The engineered immune cell of claim 3 , wherein the immune cell is an antigen presenting cell (APC).
8. The engineered immune cell of claim 1 , wherein the immune cell is a T cell.
9. The engineered immune cell of claim 2 , wherein the immune cell is a T cell.
10. The engineered immune cell of claim 3 , wherein the immune cell is a T cell.
11. The engineered immune cell of claim 1 , wherein the cell further comprises a chimeric antigen receptor (CAR).
12. The engineered immune cell of claim 1 , wherein the cell further comprises an engineered T cell receptor (TCR).
13. The engineered immune cell of claim 8 , wherein the cell further comprises a chimeric antigen receptor (CAR).
14. The engineered immune cell of claim 8 , wherein the cell further comprises an engineered T cell receptor (TCR).
15. An engineered immune cell, comprising a nucleic acid encoding an immunomodulatory protein comprising a variant CD80 polypeptide set forth in SEQ ID NO: 2276, wherein the immunomodulatory protein is secretable from the engineered cell.
16. The engineered immune cell of claim 15 , wherein the immune cell is an antigen presenting cell (APC).
17. The engineered immune cell of claim 15 , wherein the immune cell is a T cell.
18. The engineered immune cell of claim 15 , wherein the cell further comprises a chimeric antigen receptor (CAR).
19. The engineered immune cell of claim 15 , wherein the cell further comprises an engineered T cell receptor (TCR).
20. The engineered immune cell of claim 17 , wherein the cell further comprises a chimeric antigen receptor (CAR).
21. The engineered immune cell of claim 17 , wherein the cell further comprises an engineered T cell receptor (TCR).
22. A pharmaceutical composition comprising the engineered immune cell of claim 1 .
23. A pharmaceutical composition comprising the engineered immune cell of claim 2 .
24. A pharmaceutical composition comprising the engineered immune cell of claim 8 .
25. A pharmaceutical composition comprising the engineered immune cell of claim 15 .
26. A pharmaceutical composition comprising the engineered immune cell of claim 17 .
27. A pharmaceutical composition comprising the engineered immune cell of claim 20 .
28. A pharmaceutical composition comprising the engineered immune cell of claim 21 .