PSMA-Directed CAR T Cells Combined with Low-Dose Docetaxel Treatment Induce Tumor Regression in a Prostate Cancer Xenograft Model.

ABSTRACT: While chimeric antigen receptor (CAR) T cell immunotherapy targeting CD19 has shown remarkable success in patients with lymphoid malignancies, the potency of CAR T cells in solid tumors is low so far. To improve the efficacy of CAR T cells targeting prostate carcinoma, we designed a novel CAR that recognizes a new epitope in the prostate-specific membrane antigen (PSMA) and established novel paradigms to apply CAR T cells in a preclinical prostate cancer model. In vitro characterization of the D7 single-chain antibody fragment-derived anti-PSMA CAR confirmed that the choice of the co-stimulatory domain is a major determinant of CAR T cell activation, differentiation, and exhaustion. In vivo, focal injections of the PSMA CAR T cells eradicated established human prostate cancer

SUBMITTER: Alzubi J 

PROVIDER: S-EPMC7372156 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature