4-1BB Signaling Boosts the Anti-Tumor Activity of CD28-Incorporated 2^nd Generation Chimeric Antigen Receptor-Modified T Cells.

ABSTRACT: While chimeric antigen receptor-modified T (CAR-T) cells have shown great success for the treatment of B cell leukemia, their efficacy appears to be compromised in B cell derived lymphoma and solid tumors. Optimization of the CAR design to improve persistence and cytotoxicity is a focus of the current CAR-T study. Herein, we established a novel CAR structure by adding a full length 4-1BB co-stimulatory receptor to a 28Z-based second generation CAR that targets CD20. Our data indicated that this new 2028Z-4-1BB CAR-T cell showed improved proliferation and cytotoxic ability. To further understand the mechanism of action, we found that constitutive 4-1BB sensing significantly reduced the apoptosis of CAR-T cells, enhanced proliferation, and increased NF-κB pathway activation. Consistent with

SUBMITTER: Dai Q 

PROVIDER: S-EPMC7691374 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature