MND promoter chimeric antigen receptors

1. A lentiviral vector comprising a polynucleotide comprising a myeloproliferative sarcoma virus enhancer, negative control region deleted, dl587rev primer-binding site substituted (MND) promoter operably linked to a nucleic acid encoding a chimeric antigen receptor (CAR), wherein the CAR comprises:

(a) a signal peptide;

(b) an scFv that binds B cell maturation antigen (BCMA);

(c) a CD8α hinge domain as set forth in SEQ ID NO: 28;

(d) a CD8α transmembrane domain;

(e) a CD137 co-stimulatory signaling domain; and

a CD3ζ primary signaling domain.

2. The lentiviral vector of claim 1 , wherein lentiviral vector selected from the group consisting of: human immunodeficiency virus (HIV); 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 , comprising a left (5′) retroviral LTR, a Psi (Ψ) packaging signal, a central polypurine tract/DNA flap (cPPT/FLAP), a retroviral export element; the MND promoter operably linked to the CAR of claim 1 ; and a right (3′) retroviral LTR.

4. The lentiviral vector of claim 3 , further comprising:

a) a heterologous polyadenylation sequence;

b) a heterologous polyadenylation sequence that is a bovine growth hormone polyadenylation or signal rabbit β-globin polyadenylation sequence; or

c) a hepatitis B virus posttranscriptional regulatory element (HPRE) or woodchuck post-transcriptional regulatory element (WPRE).

5. The lentiviral vector of claim 3 , wherein:

a) the promoter of the 5′ LTR is replaced with a heterologous promoter;

b) the promoter of the 5′ LTR is replaced with a heterologous promoter selected from the group consisting of: a cytomegalovirus (CMV) promoter, a Rous Sarcoma Virus (RSV) promoter, or a Simian Virus 40 (SV40) promoter.

6. The lentiviral vector of claim 3 , wherein:

a) the 5′ LTR or 3′ LTR is a lentivirus LTR;

b) the 3′ LTR comprises one or more modifications;

c) the 3′ LTR comprises one or more deletions;

d) the 3′ LTR is a self-inactivating (SIN) LTR.

7. An isolated immune effector cell comprising the lentiviral vector of claim 1 .

8. The immune effector cell of claim 7 , wherein the immune effector cell is a T lymphocyte.

9. A composition comprising the immune effector cell of claim 7 and a physiologically acceptable excipient.

10. A composition comprising the immune effector cell of claim 8 and a physiologically acceptable excipient.

11. A method of making an immune effector cell comprising isolating CD34+ cells from bone marrow, cord blood or mobilized peripheral blood from a subject, and introducing the lentiviral vector of claim 1 into the isolated CD34+ cells.