Retargeting of T lymphocytes to PSCA- or PSMA positive prostate cancer cells using the novel modular chimeric antigen receptor platform technology “UniCAR”

// Anja Feldmann 1, * , Claudia Arndt 1, * , Ralf Bergmann 1, * , Simon Loff 2, 3, * , Marc Cartellieri 1, 4, * , Dominik Bachmann 2, ** , Roberta Aliperta 1, ** , Mirjam Hetzenecker 2, ** , Florian Ludwig 2, ** , Susann Albert 2, ** , Pauline Ziller-Walter 2, ** , Alexandra Kegler 1, ** , Stefanie Koristka 1, ** , Sebastian Gartner 1, ** , Marc Schmitz 5, 7, 8 , Armin Ehninger 3 , Gerhard Ehninger 2, 6, 7, 8 , Jens Pietzsch 1, 9 , Jorg Steinbach 1, 7, 8, 9 and Michael Bachmann 1, 2, 6, 7, 8 1 Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Institute of Radiopharmaceutical Cancer Research, Dresden, Germany 2 UniversityCancerCenter (UCC) ‘Carl Gustav Carus’ TU Dresden, Tumor Immunology, Dresden, Germany 3 GEMoaB Monoclonals GmbH, Dresden, Germany 4 Cellex Patient Treatment GmbH, Dresden, Germany 5 Institute of Immunology, ‘Carl Gustav Carus’, TU Dresden, Dresden, Germany 6 Medical Clinic and Policlinic I, University Hospital ‘Carl Gustav Carus’, TU Dresden, Dresden, Germany 7 German Cancer Consortium (DKTK), partner site Dresden; and German Cancer Research Center (DKFZ), Heidelberg, Germany 8 National Center for Tumor Diseases (NCT), Dresden, ‘Carl Gustav Carus’ TU Dresden, Dresden, Germany 9 Department of Chemistry and Food Chemistry, School of Science, TU Dresden, Dresden, Germany * These authors have contributed equally first to this work ** These authors have contributed equally second to this work Correspondence to: Michael Bachmann, email: M.Bachmann@hzdr.de Keywords: CAR, retargeting, T cells Received: September 02, 2016     Accepted: January 04, 2017     Published: February 21, 2017 ABSTRACT 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.