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.
Author Info: (1) Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Institute of Radiopharmaceutical Cancer Research, Dresden, Germany. (2) Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Institute of R
Author Info: (1) Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Institute of Radiopharmaceutical Cancer Research, Dresden, Germany. (2) Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Institute of Radiopharmaceutical Cancer Research, Dresden, Germany. (3) Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Institute of Radiopharmaceutical Cancer Research, Dresden, Germany. (4) UniversityCancerCenter (UCC) 'Carl Gustav Carus' TU Dresden, Tumor Immunology, Dresden, Germany. GEMoaB Monoclonals GmbH, Dresden, Germany. (5) Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Institute of Radiopharmaceutical Cancer Research, Dresden, Germany. Cellex Patient Treatment GmbH, Dresden, Germany. (6) UniversityCancerCenter (UCC) 'Carl Gustav Carus' TU Dresden, Tumor Immunology, Dresden, Germany. (7) Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Institute of Radiopharmaceutical Cancer Research, Dresden, Germany. (8) UniversityCancerCenter (UCC) 'Carl Gustav Carus' TU Dresden, Tumor Immunology, Dresden, Germany. (9) UniversityCancerCenter (UCC) 'Carl Gustav Carus' TU Dresden, Tumor Immunology, Dresden, Germany. (10) UniversityCancerCenter (UCC) 'Carl Gustav Carus' TU Dresden, Tumor Immunology, Dresden, Germany. (11) UniversityCancerCenter (UCC) 'Carl Gustav Carus' TU Dresden, Tumor Immunology, Dresden, Germany. (12) Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Institute of Radiopharmaceutical Cancer Research, Dresden, Germany. (13) Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Institute of Radiopharmaceutical Cancer Research, Dresden, Germany. (14) Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Institute of Radiopharmaceutical Cancer Research, Dresden, Germany. (15) Institute of Immunology, 'Carl Gustav Carus', TU Dresden, Dresden, Germany. German Cancer Consortium (DKTK), partner site Dresden; and German Cancer Research Center (DKFZ), Heidelberg, Germany. National Center for Tumor Diseases (NCT), Dresden, 'Carl Gustav Carus' TU Dresden, Dresden, Germany. (16) GEMoaB Monoclonals GmbH, Dresden, Germany. (17) UniversityCancerCenter (UCC) 'Carl Gustav Carus' TU Dresden, Tumor Immunology, Dresden, Germany. Medical Clinic and Policlinic I, University Hospital 'Carl Gustav Carus', TU Dresden, Dresden, Germany. German Cancer Consortium (DKTK), partner site Dresden; and German Cancer Research Center (DKFZ), Heidelberg, Germany. National Center for Tumor Diseases (NCT), Dresden, 'Carl Gustav Carus' TU Dresden, Dresden, Germany. (18) Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Institute of Radiopharmaceutical Cancer Research, Dresden, Germany. Department of Chemistry and Food Chemistry, School of Science, TU Dresden, Dresden, Germany. (19) Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Institute of Radiopharmaceutical Cancer Research, Dresden, Germany. German Cancer Consortium (DKTK), partner site Dresden; and German Cancer Research Center (DKFZ), Heidelberg, Germany. National Center for Tumor Diseases (NCT), Dresden, 'Carl Gustav Carus' TU Dresden, Dresden, Germany. Department of Chemistry and Food Chemistry, School of Science, TU Dresden, Dresden, Germany. (20) Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Institute of Radiopharmaceutical Cancer Research, Dresden, Germany. UniversityCancerCenter (UCC) 'Carl Gustav Carus' TU Dresden, Tumor Immunology, Dresden, Germany. Medical Clinic and Policlinic I, University Hospital 'Carl Gustav Carus', TU Dresden, Dresden, Germany. German Cancer Consortium (DKTK), partner site Dresden; and German Cancer Research Center (DKFZ), Heidelberg, Germany. National Center for Tumor Diseases (NCT), Dresden, 'Carl Gustav Carus' TU Dresden, Dresden, Germany.
