Functional enhancement of mesothelin-targeted TRuC-T cells by a PD1-CD28 chimeric switch receptor.

ABSTRACT: T cells expressing a mesothelin (MSLN)-specific T cell receptor fusion construct (TRuC^®), called TC-210, have demonstrated robust antitumor activity in preclinical models of mesothelioma, ovarian cancer, and lung cancer. However, they are susceptible to suppression by the programmed cell death protein 1 (PD-1)/programmed cell death protein ligand 1 (PD-L1) axis and lack intrinsic costimulatory signaling elements. To enhance the function of anti-MSLN TRuC-T cells, chimeric switch receptors (CSRs) have been designed to co-opt the immunosuppressive PD-1/PD-L1 axis and to deliver a CD28-mediated costimulatory signal. Here, we report that coexpression of the PD1-CD28 CSR in TRuC-T cells enhanced T cell receptor signaling, increased proinflammatory effector cytokines, decreased anti-i

SUBMITTER: McCarthy D 

PROVIDER: S-EPMC10700406 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature