Elimination of BCMA-positive malignancies by CAR expressing NK cells

1 . A genetically modified NK cell expressing

(i) a membrane bound recombinant chimeric antigen receptor (CAR) that comprises in a single polypeptide chain an extracellular binding domain, a hinge domain, a transmembrane domain, and a signaling domain, wherein the extracellular binding domain specifically binds to a BCMA receptor;

(ii) a recombinant CD16;

(iii) an autocrine growth stimulating cytokine; and

(iv) optionally one of IL-12, a TGF-beta trap, or a homing receptor.

2 - 7 . (canceled)

8 . The genetically modified NK cell of claim 1 wherein the IL-12 is a single chain IL-12 heterodimer.

9 . The genetically modified NK cell of claim 1 wherein the TGF-beta trap comprises a single chain dimer of the TGF-beta Receptor II ectodomain.

10 - 12 . (canceled)

13 . A genetically modified NK cell, comprising:

a recombinant nucleic acid encoding

(i) a membrane bound recombinant chimeric antigen receptor (CAR) that comprises in a single polypeptide chain an extracellular binding domain, a hinge domain, a transmembrane domain, and a signaling domain, wherein the extracellular binding domain specifically binds to a BCMA receptor;

(ii) a recombinant CD16;

(iii) an autocrine growth stimulating cytokine; and

(iv) optionally one of IL-12, a TGF-beta trap, or a homing receptor.

14 . The genetically modified NK cell of claim 13 wherein the recombinant nucleic acid is a polycistronic RNA.

15 . The genetically modified NK cell of claim 13 wherein the NK cell is an NK-92 cell.

16 . The genetically modified NK cell of claim 13 wherein the extracellular binding domain comprises a scFv.

17 . The genetically modified NK cell of claim 13 wherein the signaling domain comprises a FcεRIγ signaling domain or a CD3ζ signaling domain.

18 . The genetically modified NK cell of claim 13 wherein the recombinant CD16 is a CD1 6 158V mutant.

19 . The genetically modified NK cell of claim 13 wherein the autocrine growth stimulating cytokine is IL-2 or IL-15.

20 . The genetically modified NK cell of claim 19 wherein the autocrine IL-2 or IL-15 further comprises an endoplasmic retention sequence.

21 . The genetically modified NK cell of claim 13 wherein the IL-12 is a single chain IL-12 heterodimer.

22 . The genetically modified NK cell of claim 13 wherein the TGF-beta trap comprises a single chain dimer of the TGF-beta Receptor II ectodomain.

23 . The genetically modified NK cell of claim 22 wherein the TGF-beta trap is a secreted form of a single chain dimer of the TGF-beta Receptor II ectodomain.

24 . The genetically modified NK cell of claim 13 wherein the homing receptor is a cell adhesion molecule, a selectin, an integrin, a C—C chemokine receptor, or C—X—C chemokine receptor.

25 . The genetically modified NK cell of claim 24 wherein the homing receptor is selected from the group consisting of CCR1, CCR2, CCR3, CCR4, CCR5, CCR6, CCR7, CCR8, CCR9, CCR10, CXCR1, CXCR2, CXCR3, CXCR4, CXCR5, CXCR6, CXCR7, CX3CR1, XCR1, CCXCKR, D6, DARC, and a receptor for CXCL14.

26 . A method of treating cancer in a patient in need thereof, comprising administering to the patient a therapeutically effective amount of any one of the genetically modified NK cells of claim 1 or claim 13 , thereby treating the cancer.

27 . The method of claim 26 further comprising a step of administering at least one additional therapeutic entity selected from the group consisting of a viral cancer vaccine, a bacterial cancer vaccine, a yeast cancer vaccine, N-803, an antibody, a stem cell transplant, and a tumor targeted cytokine.

28 . The method of claim 26 , wherein the cancer is multiple myeloma or Hodgkin lymphoma.

29 . The method of claim 26 , wherein about 1×10 8 to about 1×10 11 cells per m 2 of body surface area of the patient are administered to the patient.

30 . (canceled)