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 the amino acid sequence set forth in SEQ ID NO: 9 encoded by the polynucleotide sequence set forth in SEQ ID NO: 10.
2. A vector comprising the polynucleotide encoding the CAR of claim 1 .
3. The vector of claim 2 , wherein the vector is an expression vector.
4. The vector of claim 2 , wherein the vector is an episomal vector.
5. The vector of claim 2 , wherein the vector is a viral vector.
6. The vector of claim 2 , wherein the vector is a retroviral vector.
7. The vector of claim 2 , wherein the vector is a lentiviral vector.
8. The vector of claim 2 , wherein the lentiviral vector is selected from the group consisting essentially of: human immunodeficiency virus 1 (HIV-1); human immunodeficiency virus 2 (HIV-2), visna-maedi virus (VMV) virus; caprine arthritis-encephalitis virus (CAEV); equine infectious anemia virus (EIAV); feline immunodeficiency virus (FIV); bovine immune deficiency virus (BIV); and simian immunodeficiency virus (SIV).
9. The vector of claim 8 , comprising a left (5′) retroviral 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.
10. The vector of claim 9 , further comprising a heterologous polyadenylation sequence.
11. The vector of claim 10 , wherein the polyadenylation sequence is a bovine growth hormone polyadenylation or signal rabbit β-globin polyadenylation sequence.
12. The vector of claim 9 , wherein the promoter of the 5′ LTR is replaced with a heterologous promoter.
13. The vector of claim 12 , wherein the heterologous promoter is a cytomegalovirus (CMV) promoter, a Rous Sarcoma Virus (RSV) promoter, or a Simian Virus 40 (SV40) promoter.
14. The vector of claim 9 , wherein the 5′ LTR or 3′ LTR is a lentivirus LTR.
15. The vector of claim 9 , wherein the 3′ LTR comprises one or more modifications.
16. The vector of claim 9 , wherein the 3′ LTR comprises one or more deletions.
17. The vector of claim 9 , wherein the 3′ LTR is a self-inactivating (SIN) LTR.
18. The vector of claim 9 , 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, d1587rev primer-binding site substituted (MND) promoter.
19. An immune effector cell expressing the CAR of claim 1 .
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 20 and a physiologically acceptable excipient.
22. An immune effector cell comprising the vector of claim 2 .
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 23 and a physiologically acceptable excipient.
25. An immune effector cell comprising the vector of claim 5 .
26. The immune effector cell of claim 25 , wherein the immune effector cell is selected from the group consisting of: a T lymphocyte and a natural killer (NK) cell.
27. A composition comprising the immune effector cell of claim 26 and a physiologically acceptable excipient.
28. An immune effector cell comprising the vector of claim 6 .
29. The immune effector cell of claim 28 , wherein the immune effector cell is selected from the group consisting of: a T lymphocyte and a natural killer (NK) cell.
30. A composition comprising the immune effector cell of claim 29 and a physiologically acceptable excipient.