Research ArticleCancer

SynNotch-CAR T cells overcome challenges of specificity, heterogeneity, and persistence in treating glioblastoma

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Science Translational Medicine  28 Apr 2021:
Vol. 13, Issue 591, eabe7378
DOI: 10.1126/scitranslmed.abe7378

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Short circuiting solid tumors

Two major hurdles in chimeric antigen receptor (CAR) T cell therapy for solid tumors are ensuring specificity to tumor cells without affecting healthy cells and avoiding tumor escape due to antigen loss. To address these challenges, Hyrenius-Wittsten et al. and Choe et al. developed synthetic notch (synNotch)–CAR T cells targeting solid tumor antigens and used them to treat mouse models of mesothelioma, ovarian cancer, and glioblastoma. In both studies, the authors demonstrated that synNotch-CAR T cells were better at controlling tumors than traditional CAR T cells and did not result in toxicity or damage to healthy tissue. These results suggest that synNotch-CAR T cells may be an effective treatment strategy for solid tumors.

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