Sensitive and adaptable pharmacological control of CAR T cells through extracellular receptor dimerization.

ABSTRACT: Chimeric antigen receptor (CAR) T cell therapies have achieved promising outcomes in several cancers, however more challenging oncology indications may necessitate advanced antigen receptor designs and functions. Here we describe a bipartite receptor system comprised of separate antigen targeting and signal transduction polypeptides, each containing an extracellular dimerization domain. We demonstrate that T cell activation remains antigen dependent but can only be achieved in the presence of a dimerizing drug, rapamycin. Studies performed in vitro and in xenograft mouse models illustrate equivalent to superior anti-tumor potency compared to currently used CAR designs, and at rapamycin concentrations well below immunosuppressive levels. We further show that the extracellular positioning of

SUBMITTER: Leung WH 

PROVIDER: S-EPMC6629089 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature