Incorporation of a hinge domain improves the expansion of chimeric antigen receptor T cells.

ABSTRACT:

Background

Multiple iterations of chimeric antigen receptors (CARs) have been developed, mainly focusing on intracellular signaling modules. However, the effect of non-signaling extracellular modules on the expansion and therapeutic efficacy of CARs remains largely undefined.

Methods

We generated two versions of CAR vectors, with or without a hinge domain, targeting CD19, mesothelin, PSCA, MUC1, and HER2, respectively. Then, we systematically compared the effect of the hinge domains on the growth kinetics, cytokine production, and cytotoxicity of CAR T cells in vitro and in vivo.

Results

During in vitro culture period, the percentages and absolute numbers of T cells expressing the CARs containing a hinge domain continuously increased, mainly through the promotion of C

SUBMITTER: Qin L 

PROVIDER: S-EPMC5347831 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature