28 April 2021
Vol 13, Issue 591

About The Cover

Cover image expansion

ONLINE COVER Taking CAR T Cells Up a Notch. This image shows three sections of a glioblastoma tumor (yellow, lower image) in a mouse brain (nuclei in blue) infiltrated with activated synthetic notch-chimeric antigen receptor (synNotch-CAR) T cells (cyan, upper image) and undergoing apoptosis (magenta, middle image). Tumor specificity and effector cell exhaustion are two challenges hindering the success of CAR T cells for solid tumors. In a pair of manuscripts, Choe et al. and Hyrenius-Wittsten et al. demonstrated that synNotch-CAR T cells, which only turn on expression of the CAR at the site of the tumor, were tumor-specific and kept CAR T cells in a less exhausted state. synNotch-CAR T cell treatment reduced tumor burden in mouse models of glioblastoma, mesothelioma, and ovarian cancer. Thus, synNotch-CAR T cells are an attractive option for overcoming challenges associated with treating solid tumors. [CREDIT: CHOE ET AL./SCIENCE TRANSLATIONAL MEDICINE]