Immune cell compositions and methods of use

A T cell comprising a transgene, which transgene comprises a first nucleotide sequence encoding a dominant negative form of an inhibitor of a cell-mediated immune response of the T cell, wherein expression of the transgene is under control of an inducible promoter, which inducible promoter is induced upon activation of the T cell.

A T cell comprising a transgene, which transgene comprises a first nucleotide sequence encoding an immunomodulatory agent, wherein expression of the transgene is under control of an inducible promoter, which inducible promoter is induced upon activation of the T cell, wherein the immunomodulatory agent is a single chain variable fragment (scFv) or peptide antibody, which immunomodulatory agent binds to and inhibits an immune checkpoint inhibitor.

An immunostimulatory cell comprising in one or more transgenes:

• (a) a first nucleotide sequence encoding a chimeric antigen receptor (CAR), wherein the CAR binds to a target antigen associated with a mammalian disease or disorder, (b) a second nucleotide sequence encoding a dominant negative form of an inhibitor of a cell-mediated immune response of the immunostimulatory cell, and (c) a third a nucleotide sequence encoding a membrane bound form of interleukin 12 (membrane IL-12).

An immunostimulatory cell comprising:

• (1) in one or more transgenes:
• (a) a first nucleotide sequence encoding a chimeric antigen receptor (CAR), wherein the CAR binds to a target antigen associated with a mammalian disease or disorder, (b) a second nucleotide sequence encoding a dominant negative form of an inhibitor of a cell-mediated immune response of the immunostimulatory cell, that is a receptor-synthetic Notch fusion protein comprising (i) an extracellular domain of the inhibitor of a cell-mediated immune response of the immunostimulatory cell, (ii) the transmembrane core domain of Notch C-terminal to the extracellular domain, and (iii) a transcription factor C-terminal to the transmembrane core domain of Notch, and (2) in a different transgene (c) a third nucleotide sequence encoding a membrane bound form of interleukin 12 (membrane IL-12), wherein expression of the membrane IL-12 is under control of an inducible promoter, which inducible promoter is induced upon binding of the transcription factor, and wherein the transcription factor is cleaved from the receptor-synthetic Notch fusion protein intracellularly upon binding of the extracellular domain to its ligand.

An immunostimulatory cell comprising in one or more transgenes:

• (a) a first nucleotide sequence encoding a dominant negative form of an inhibitor of a cell-mediated immune response of the immunostimulatory cell, and (b) a second nucleotide sequence encoding interleukin 12 (IL-12), wherein the IL-12 when expressed by the immunostimulatory cell is secreted from the immunostimulatory cell.

The immunostimulatory cell of claim 88, wherein the pathogen is a human pathogen.