Methods and compositions for modulating arginine levels in immune cells

An expression vector comprising an isolated nucleic acid encoding a) an antigen-specific targeting region, b) a transmembrane domain, c) optionally at least one co-stimulatory domain, d) an intracellular signaling domain and e) an arginine transporter.

A pharmaceutical composition comprising a chimeric antigen receptor T cell (CAR-T cell) which expresses a recombinant arginine transporter and a chimeric antigen receptor protein.

A method for treating a condition in a human patient in need thereof, comprising:

• administering to the human patient a therapeutically effective amount of a composition comprising a chimeric antigen receptor T cell (CAR-T cell) which expresses a recombinant arginine transporter and a chimeric antigen receptor protein.

A method of modulating a T cell-mediated immune response to a target cell population expressing a cell surface antigen in a patient in need thereof, comprising administering to the patient a therapeutically effective amount of T-cells that are a) genetically modified to express a chimeric antigen receptor wherein the chimeric antigen receptor comprises:

• at least one antigen-specific targeting region that specifically binds the cell surface antigen present on the target cell population, a transmembrane domain, an intracellular signaling domain, and b) genetically modified to express a recombinant arginine transporter.

A method of making a genetically modified CAR-T cell that expresses a recombinant arginine transporter, comprising:

• transfecting a T-cell with a DNA construct comprising a nucleotide sequence for a specific chimeric antigen receptor and for an arginine transporter thereby producing a genetically modified CAR-T cell that expresses both the chimeric antigen receptor and the arginine transporter;
• and
• culturing the genetically modified CAR-T cell in a culture medium comprising arginine.

A genetically modified T-cell genetically modified to express a recombinant arginine transporter.

A pharmaceutical composition comprising a T cell which expresses a recombinant arginine transporter protein.

A method for treating a condition in a human patient in need thereof, comprising:

• administering to the human patient a therapeutically effective amount of a composition comprising a T cell which expresses a recombinant arginine transporter.

A method of making a genetically modified T cell that expresses a recombinant arginine transporter, comprising:

• transfecting a T-cell with a DNA construct comprising a nucleotide sequence for an arginine transporter thereby producing a genetically modified T cell that expresses the arginine transporter;
• and
• culturing the genetically modified T cell in a culture medium comprising arginine.

A method of increasing T cell survival in a low arginine environment, the method comprising:

• administering a T cell comprising a recombinant arginine transporter to a low arginine environment.