BCMA chimeric antigen receptors
The invention provides improved compositions for adoptive T cell therapies for B cell related conditions.
1. A lentiviral vector comprising a left (5′) lentiviral LTR wherein the promoter of the 5′ LTR is replaced with a CMV promoter; a Psi (Ψ) packaging signal; a cPPT/FLAP; a Rev response element (RRE); a myeloproliferative sarcoma virus enhancer, negative control region deleted, dl587rev primer-binding site substituted (MND) promoter operably linked to a polynucleotide sequence encoding a chimeric antigen receptor (CAR), wherein the polynucleotide sequence is set forth in SEQ ID NO: 10; a right (3′) lentiviral self-inactivating (SIN) LTR; and a heterologous polyadenylation sequence.
2. The lentiviral vector of claim 1 , 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).
3. The lentiviral vector of claim 1 , wherein the heterologous polyadenylation sequence is a bovine growth hormone polyadenylation signal or a rabbit β-globin polyadenylation sequence.
4. An immune effector cell comprising the lentiviral vector of claim 1 .
5. The immune effector cell of claim 4 , wherein the immune effector cell is selected from the group consisting of: a T lymphocyte and a natural killer (NK) cell.
6. A composition comprising the immune effector cell of claim 5 .
7. A composition comprising the immune effector cell of claim 5 and a physiologically acceptable excipient.
8. An immune effector cell comprising the lentiviral vector of claim 2 .
9. The immune effector cell of claim 8 , wherein the immune effector cell is selected from the group consisting of: a T lymphocyte and a natural killer (NK) cell.
10. A composition comprising the immune effector cell of claim 9 .
11. A composition comprising the immune effector cell of claim 9 and a physiologically acceptable excipient.
12. An immune effector cell comprising the lentiviral vector of claim 3 .
13. The immune effector cell of claim 12 , wherein the immune effector cell is selected from the group consisting of: a T lymphocyte and a natural killer (NK) cell.
14. A composition comprising the immune effector cell of claim 13 .
15. A composition comprising the immune effector cell of claim 13 and a physiologically acceptable excipient.