B7-H3-mediated reversal of CAR-T cell exhaustion induces a notable antitumour response in ovarian cancer models.

ABSTRACT:

Background

Functional CAR-T cell exhaustion in the immunosuppressive tumour microenvironment remains the main barrier to the success of CAR-T cell therapy for treating solid tumours. Mesothelin (MSLN) has emerged as an attractive target for CAR-T cell therapy for several solid malignancies, including ovarian cancer. In this study, we aimed to investigate the role and mechanism of lipid metabolites in anti-MSLN CAR-T cell exhaustion in ovarian cancer cells.

Methods

We engineered anti-MSLN CAR-T cells targeting ovarian cancer cells with high MSLN expression as a pivotal tool for in vitro and in vivo experiments. Moreover, liquid chromatography-tandem mass spectrometry (LC-MS/MS) revealed the critical role of oxylipin 12-HETE in the exhaustion of CAR-T cells. By employing struc

SUBMITTER: Liu Q 

PROVIDER: S-EPMC12539249 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature