Blocking TCR restimulation induced necroptosis in adoptively transferred T cells improves tumor control.

ABSTRACT: Advancements in adoptive cell transfer therapy (ACT) has led to the use of T cells engineered with tumor specific T cell receptors, which after rapid expansion can be obtained in sufficient numbers for treating patients. However, due to massive proliferation these cells are close to replicative senescence, exhibit exhausted phenotype, and also display increased susceptibility to activation induced cell death. We have previously shown that tumor reactive T cells undergo caspase-independent cell death upon TCR restimulation with cognate antigen, which involves reactive oxygen species and c-jun N-terminal kinase. Herein, we show that a large fraction of the human melanoma epitope tyrosinase reactive TCR transduced T cells that exhibit effector memory (TEM) phenotype and undergo programmed nec

SUBMITTER: Kesarwani P 

PROVIDER: S-EPMC5342484 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature