Chimeric antigen receptors and methods of making
Provided are methods of generating chimeric antigen receptors (CAR). In some embodiments, library screening of CAR is performed by generating a vector encoding the CAR from random attachment of vectors from libraries of vectors encoding antigen-binding domains (e.g., scFv regions), hinge regions, and endodomains. In some embodiments, the vectors contain a transposon.
1. A polypeptide encoded by a nucleic acid sequence comprising nucleotides 67-1485 of SEQ ID NO: 5.
2. The polypeptide of claim 1 , wherein the nucleic acid sequence comprises nucleotides 1-1485 of SEQ ID NO: 5.
3. The polypeptide of claim 1 , wherein the nucleic acid sequence comprises SEQ ID NO: 5.
4. A T cell comprising the polypeptide of claim 1 .
5. The T cell of claim 4 , wherein the T cell is an alpha beta T cell, a gamma delta T cell, or an NKT cell.
6. The T cell of claim 4 , further comprising a membrane-bound cytokine.
7. The T cell of claim 6 , wherein the membrane-bound cytokine is membrane-bound IL-15.
8. A pharmaceutical preparation comprising the T cell of claim 4 .
9. A method of treating a B-cell malignancy in a human subject in need thereof, the method comprising administering the T cell of claim 4 to the human subject.
10. The method of claim 9 , wherein the B-cell malignancy is a lymphoma or a leukemia.
11. A nucleic acid comprising nucleotides 67-1485 of SEQ ID NO: 5.
12. The nucleic acid of claim 11 , wherein the nucleic acid comprises nucleotides 1-1485 of SEQ ID NO:5.
13. A transposon comprising the nucleic acid of claim 11 .
14. A T cell comprising the nucleic acid of claim 11 .
15. The T cell of claim 14 , wherein the T cell is an alpha beta T cell, a gamma delta T cell, or an NKT cell.
16. The T cell of claim 14 , further comprising a membrane-bound cytokine.
17. The T cell of claim 16 , wherein the membrane-bound cytokine is membrane-bound IL-15.
18. A pharmaceutical preparation comprising the T cell of claim 14 .
19. A method of treating a B-cell malignancy in a human subject in need thereof, the method comprising administering the T cell of claim 14 to the human subject.
20. The method of claim 19 , wherein the B-cell malignancy is a lymphoma or a leukemia.