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Chimeric antigen receptor (CAR)-expressing T cells lacking negative regulators of T cell receptor (TCR) signaling

CAR-expressing T cells that lack negative regulators of TCR signaling could be useful as antitumor T cell therapies. Diacylglycerol kinases (DGKs) are known negative regulators of TCR signaling. In a xenograft mouse model for established human mesothelioma, CAR-expressing murine T cells that lacked DGKs significantly decreased tumor growth compared with cells that expressed DGKs (p<0.05). Next steps include developing human CAR-expressing T cells that also express DGK-targeting small interfering RNAs or dominant negative forms of DGKs.

SciBX 6(17); doi:10.1038/scibx.2013.425
Published online May 2, 2013

Patent application filed; available for licensing through the University of Pennsylvania's Center for Technology Transfer

Riese, M.J. et al. Cancer Res.;
published online April 10, 2013;
Contact: Steven M. Albelda, University of Pennsylvania, Philadelphia, Pa.