SynNotch CAR circuits enhance solid tumor recognition and promote persistent antitumor activity in mouse models.

ABSTRACT: The first clinically approved engineered chimeric antigen receptor (CAR) T cell therapies are remarkably effective in a subset of hematological malignancies with few therapeutic options. Although these clinical successes have been exciting, CAR T cells have hit roadblocks in solid tumors that include the lack of highly tumor-specific antigens to target, opening up the possibility of life-threatening "on-target/off-tumor" toxicities, and problems with T cell entry into solid tumor and persistent activity in suppressive tumor microenvironments. Here, we improve the specificity and persistent antitumor activity of therapeutic T cells with synthetic Notch (synNotch) CAR circuits. We identify alkaline phosphatase placental-like 2 (ALPPL2) as a tumor-specific antigen expressed in a spectrum of s

SUBMITTER: Hyrenius-Wittsten A 

PROVIDER: S-EPMC8594452 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature