Regulation of CAR T cell-mediated cytokine release syndrome-like toxicity using low molecular weight adapters.

ABSTRACT: Although chimeric antigen receptor (CAR) T cell therapies have demonstrated considerable success in treating hematologic malignancies, they have simultaneously been plagued by a cytokine release syndrome (CRS) that can harm or even kill the cancer patient. We describe a CAR T cell strategy in which CAR T cell activation and cancer cell killing can be sensitively regulated by adjusting the dose of a low molecular weight adapter that must bridge between the CAR T cell and cancer cell to initiate tumor eradication. By controlling the concentration and dosing schedule of adapter administration, we document two methods that can rapidly terminate (<3 h) a pre-existing CRS-like toxicity and two unrelated methods that can pre-emptively prevent a CRS-like toxicity that would have otherwise occurred

SUBMITTER: Lee YG 

PROVIDER: S-EPMC6581910 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature