Compositions and methods for inhibiting T cell exhaustion
AssigneeThe Board of Trustees of the Leland Stanford Junior University
InventorsCrystal L. Mackall, Rachel Lynn, Evan Weber, Elena Sotillo
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Abstract
The present invention relates to T cell compositions and methods of using the same in the context of therapy and treatment. In particular, the invention provides T cells that are modified (e.g., genetically and/or functionally) to maintain functionality under conditions in which unmodified T cells display exhaustion. Compositions and methods disclosed herein find use in preventing exhaustion of engineered (e.g., chimeric antigen receptor (CAR) T cells) as well as non-engineered T cells thereby enhancing T cell function (e.g., activity against cancer or infectious disease).
Claims20
A method of preparing T cells that are less susceptible to exhaustion, comprising modifying T cells by introducing into them a nucleic acid encoding human c-Jun and a nucleic acid encoding an engineered receptor specific for a tumor antigen, wherein the engineered receptor is a chimeric antigen receptor (CAR) or an engineered T-cell receptor (TCR),
- wherein the human c-Jun and the engineered receptor are expressed from separate expression vectors or wherein the human c-Jun and the engineered receptor are co-expressed from a single expression vector as separate polypeptides, and
- wherein the modified T cells exhibit a Th1 cytokine profile.
Dependencies are inferred from the claim text.