Inducible Gene Switches with Memory in Human T Cells for Cellular Immunotherapy.

ABSTRACT: Cell-based therapies that employ engineered T cells-including those modified to express chimeric antigen receptors (CARs)-to target cancer cells have demonstrated promising responses in clinical trials. However, engineered T cell responses must be regulated to prevent severe side effects such as cytokine storms and off-target responses. Here we present a class of recombinase-based gene circuits that will enable inducible, one-time state switching in adoptive T cell therapy using an FDA-approved drug, creating a generalizable platform that can be used to control when and how strongly a gene is expressed. These circuits exhibit memory such that induced T cells will maintain any changes made even when the drug inducer is removed. This memory feature avoids prolonged drug inducer exposure, thu

SUBMITTER: Chakravarti D 

PROVIDER: S-EPMC6703182 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature