US 12,180,283 B2 · Anti-B7-H4 chimeric antigen receptor-modified NK-92 cells

Abstract

Recombinant NK cells, and particularly recombinant NK-92 cells express an anti-B7-H4 chimeric antigen receptor (CAR) having an intracellular domain of FcεRIγ. Most notably, CAR constructs with an intracellular domain of FcεRIγ had a significantly extended duration of expression and cytotoxicity over time. The anti-B7-H4 CAR may be expressed from RNA and DNA, preferably from a tricistronic construct that further encodes CD16 and a cytokine to confer autocrine growth support. Advantageously, such constructs also enable high levels of transfection and expression of the recombinant proteins and provide a convenient selection marker to facilitate rapid production of recombinant NK/NK-92 cells.

Claims21

Dependent claims

A genetically modified anti-B7-H4 CAR NK cell, comprising:

a recombinantly expressed cytokine, wherein the recombinantly expressed cytokine comprises IL-2 or IL-15;
a recombinantly expressed CD16;
a membrane bound recombinantly expressed anti-B7-H4 chimeric antigen receptor (CAR) that comprises in a single polypeptide chain an extracellular binding domain, a hinge domain, a transmembrane domain, and a FcεRIγ signaling domain, wherein the extra cellular binding domain comprises an anti-B7-H4 scFv comprising SEQ ID NO:
21, and wherein the anti-B7-H4 CAR has at least 90% sequence homology to amino acid sequence of SEQ ID NO:1;
wherein the recombinantly expressed cytokine, the recombinantly expressed CD16, and the anti-B7-H4 CAR are expressed from an expression cassette of a plasmid that is transfected into the NK cell;
and
wherein the NK cell is an NK-92 cell.

4 more elements

Dependencies are inferred from the claim text.

Anti-B7-H4 chimeric antigen receptor-modified NK-92 cells

Life of this patent

Anti-B7-H4 chimeric antigen receptor-modified NK-92 cells

Life of this patent

Abstract

Claims21