Bifunctional Cysteine-Engineered CAR‑T Cells Enable Thiol-Mediated Targeting to Overcome Antigen Escape in B Cell Lymphoma.

ABSTRACT: Chimeric antigen receptor (CAR) T cell therapy has revolutionized the treatment of hematologic malignancies; however, durable remissions remain limited due to antigen-negative cancer relapse, where tumor cells downregulate or lose the targeted antigen to evade immune recognition. To address this challenge, we developed cysteine-engineered CAR (CysCAR) T cells that redirect T cells to target cancer cells based on extracellular redox imbalances and the altered thiol/disulfide ratios, a marker we identified on B cell lymphomas. Here, we show that CysCAR-T cells, engineered with different cysteine-modified antibody fragments, exhibit a potent and specific cytotoxicity in vitro across various B cell lymphoma (BCL) subtypes, even in antigen escape models. Moreover, by integrating cysteine

SUBMITTER: Luhle J 

PROVIDER: S-EPMC12550615 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature