BCMA chimeric antigen receptors
The invention provides improved compositions for adoptive T cell therapies for B cell related conditions.
1. A chimeric antigen receptor (CAR) comprising amino acids 22-493 of the amino acid sequence set forth in SEQ ID NO: 9.
2. A polynucleotide encoding a CAR comprising amino acids 22-493 of the amino acid sequence set forth in SEQ ID NO: 9.
3. A vector comprising a polynucleotide encoding a CAR comprising amino acids 22-493 of the amino acid sequence set forth in SEQ ID NO: 9.
4. The vector of claim 3 , wherein the vector is an expression vector, an episomal vector, a viral vector, a retroviral vector, or a lentiviral vector.
5. The vector of claim 3 , wherein the vector is a lentiviral vector selected from the group consisting of: human immunodeficiency virus 1 (HIV-1); human immunodeficiency virus 2 (HIV-2); visna-maedi virus (VMV); caprine arthritis-encephalitis virus (CAEV); equine infectious anemia virus (EIAV); feline immunodeficiency virus (FIV); bovine immune deficiency virus (BIV); and simian immunodeficiency virus (SIV).
6. The vector of claim 4 , comprising a left (5′) retroviral long terminal repeat (LTR); a Psi (Ψ) packaging signal; a central polypurine tract/DNA flap (cPPT/FLAP); a retroviral export element; a promoter operably linked to the polynucleotide encoding the CAR; and a right (3′) retroviral LTR.
7. The vector of claim 6 , further comprising a heterologous polyadenylation sequence.
8. The vector of claim 7 , wherein the heterologous polyadenylation sequence is a bovine growth hormone polyadenylation signal or a rabbit β-globin polyadenylation sequence.
9. The vector of claim 6 , wherein the promoter of the 5′ LTR is replaced with a heterologous promoter.
10. The vector of claim 9 , wherein the heterologous promoter is a cytomegalovirus (CMV) promoter, a Rous Sarcoma Virus (RSV) promoter, or a Simian Virus 40 (SV40) promoter.
11. The vector of claim 6 , wherein the 5′ LTR or 3′ LTR is a lentivirus LTR.
12. The vector of claim 6 , wherein the 3′ LTR comprises one or more modifications.
13. The vector of claim 6 , wherein the 3′ LTR comprises one or more deletions.
14. The vector of claim 6 , wherein the 3′ LTR is a self-inactivating (SIN) LTR.
15. The vector of claim 6 , wherein the promoter operably linked to the polynucleotide encoding the CAR is selected from the group consisting of: a cytomegalovirus immediate early gene promoter (CMV), an elongation factor 1 alpha promoter (EF1-α), a phosphoglycerate kinase-1 promoter (PGK), a ubiquitin-C promoter (UBQ-C), a cytomegalovirus enhancer/chicken beta-actin promoter (CAG), polyoma enhancer/herpes simplex thymidine kinase promoter (MC1), a beta actin promoter (β-ACT), a simian virus 40 promoter (SV40), and a myeloproliferative sarcoma virus enhancer, negative control region deleted, dl587rev primer-binding site substituted (MND) promoter.
16. An immune effector cell expressing the CAR of claim 1 .
17. The immune effector cell of claim 16 , wherein the immune effector cell is selected from the group consisting of: a T lymphocyte and a natural killer (NK) cell.
18. A composition comprising the immune effector cell of claim 16 and a physiologically acceptable excipient.
19. An immune effector cell comprising the polynucleotide of claim 2 .
20. The immune effector cell of claim 19 , wherein the immune effector cell is selected from the group consisting of: a T lymphocyte and a natural killer (NK) cell.
21. A composition comprising the immune effector cell of claim 19 and a physiologically acceptable excipient.
22. An immune effector cell comprising the vector of claim 3 .
23. The immune effector cell of claim 22 , wherein the immune effector cell is selected from the group consisting of: a T lymphocyte and a natural killer (NK) cell.
24. A composition comprising the immune effector cell of claim 22 and a physiologically acceptable excipient.
25. The immune effector cell of claim 17 , wherein the immune effector cell is a T lymphocyte.
26. The immune effector cell of claim 20 , wherein the immune effector cell is a T lymphocyte.
27. The immune effector cell of claim 23 , wherein the immune effector cell is a T lymphocyte.
28. The immune effector cell of claim 25 , wherein the T lymphocyte is a human T lymphocyte.
29. The immune effector cell of claim 26 , wherein the T lymphocyte is a human T lymphocyte.
30. The immune effector cell of claim 27 , wherein the T lymphocyte is a human T lymphocyte.