Sense-and-Respond Payload Delivery Using a Novel Antigen-Inducible Promoter Improves Suboptimal CAR-T Activation.

ABSTRACT: Chimeric antigen receptor (CAR)-T cell therapies demonstrate the clinical potential of lymphocytes engineered with synthetic properties. However, CAR-T cells are ineffective in most solid tumors, partly due to inadequate activation of the infused lymphocytes at the site of malignancy. To selectively enhance antitumor efficacy without exacerbating off-target toxicities, CAR-T cells can be engineered to preferentially deliver immunostimulatory payloads in tumors. Here, we report a novel antigen-inducible promoter for conditional payload expression in primary human T cells. In therapeutic T cell models, the novel NR4A-based promoter induced higher reporter gene expression than the conventional NFAT-based promoter under weakly immunogenic conditions, where payload expression is most needed. Mi

SUBMITTER: Guo T 

PROVIDER: S-EPMC9016769 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature