To develop safer CAR T cells, Feldmann et al. describe a modular CAR system that utilizes an inert “UniCAR” directed to an artificial peptide epitope. “UniCAR” T cells can be turned on to attack tumor cells by co-delivery of a tumor cell-targeting scFv coupled to the artificial peptide. As the scFv clears rapidly from circulation, the active UniCAR can rapidly become inert once infusion of the scFv is halted.
New treatment options especially of solid tumors including for metastasized prostate cancer (PCa) are urgently needed. Recent treatments of leukemias with chimeric antigen receptors (CARs) underline their impressive therapeutic potential. However CARs currently applied in the clinics cannot be repeatedly turned on and off potentially leading to severe life threatening side effects. To overcome these problems, we recently described a modular CAR technology termed UniCAR: UniCAR T cells are inert but can be turned on by application of one or multiple target modules (TMs). Here we present preclinical data summarizing the retargeting of UniCAR T cells to PCa cells using TMs directed to prostate stem cell- (PSCA) or/and prostate specific membrane antigen (PSMA). In the presence of the respective TM(s), we see a highly efficient target-specific and target-dependent activation of UniCAR T cells, secretion of pro-inflammatory cytokines, and PCa cell lysis both in vitro and experimental mice.