Chimeric antigen receptors containing the OX40 signalling domain enhance the persistence of T cells even under repeated stimulation with multiple myeloma target cells.

ABSTRACT: Persistence of CAR-T cell function is associated with relapse rate after CAR-T therapy, while co-stimulatory agents are highly concerned with the persistence of CAR-T cells. In this study, we designed and constructed a series of BCMA-targeting second-generation CAR constructs containing CD28, 41BB, and OX40 molecules, respectively, to identify the costimulatory domains most favorable for persistence. The results of routine in vitro studies showed that OX40-CAR-T and 41BB-CAR-T had similar antitumor effects and were superior to CD28-CAR-T in terms of proliferation and cytotoxicity. Although difficult to distinguish by conventional functional assays, OX40-CAR-T cells exhibited greater proliferation and enhanced immune memory than 41BB-CAR-T cells with the repeated stimulation assay by BCMA-e

SUBMITTER: Tan J 

PROVIDER: S-EPMC8974082 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature