Research ArticleCancer

TCR engagement negatively affects CD8 but not CD4 CAR T cell expansion and leukemic clearance

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Science Translational Medicine  22 Nov 2017:
Vol. 9, Issue 417, eaag1209
DOI: 10.1126/scitranslmed.aag1209

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A tale of two receptors

Although there has been an explosion of research on chimeric antigen receptor (CAR) T cell therapy, most preclinical studies use transduced human T cells in immunodeficient mice so that the clinical products can be evaluated. However, the endogenous T cell receptors (TCRs) on the human cells are unable to be activated by peptides presented in mouse MHC. To determine how CAR activity is affected by TCR engagement, Yang et al. used a CAR targeting CD19 and multiple types of transgenic T cells in immunocompetent mice. Exposure of CD8 CAR T cells to the antigen recognized by the TCR led to T cell exhaustion, apoptosis, and lack of efficacy; this phenomenon was not observed for CD4 CAR T cells. Their findings demonstrate how considering T cell biology could further improve CAR T cell therapy.