Chimeric antigen receptor clustering via cysteines enhances T-cell efficacy against tumor.

ABSTRACT: Chimeric antigen receptor (CAR) T-cell therapy achieves great success for hematological malignancies. However, clinical trials have revealed some limitations in both improving the efficacy and reducing the relapse, which calls for innovative strategies to engineer more powerful CAR-T cells. Promoting the formation of CAR clusters provides an alternative approach and potentially improves current CAR T-cell therapy against cancers. Here, we generated CAR_Cys-T cells using a 4-1BB-derived hinge region including 11 cysteines residues. The cysteines in the hinge were found to facilitate CAR_Cys clustering upon antigen stimulation and promote the antitumor activity of CAR-T cells. Compared with most conventionally used CAR-T cells with CD8α-derived hinge (CAR_conv-T

SUBMITTER: Wang Y 

PROVIDER: S-EPMC10992513 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature