MARC, a novel modular chimeric antigen receptor, improves T cell-based cancer immunotherapies by preventing early T cell exhaustion and enhancing persistence.

ABSTRACT:

Background

Chimeric antigen receptor T cell (CAR-T)-based immunotherapies have reshaped the therapeutic landscape of cancer treatment, in particular for patients afflicted with leukemia. However, defects in CAR behaviors and clinical complications have hindered their widespread application across diverse cancer types. Chief among these defects is high tonic signaling, absent in native activating immune receptors, which accelerates T cell exhaustion and undermines treatment efficacy. We hypothesized that these limitations arise because current CAR architectures fail to replicate the modular design of native activating immune receptors, which integrate distinct receptor and signaling modules. This modular assembly is crucial for maintaining proper receptor regulation and function.

SUBMITTER: Tual M 

PROVIDER: S-EPMC12010287 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature