Retargeting of T lymphocytes to PSCA- or PSMA positive prostate cancer cells using the novel modular chimeric antigen receptor platform technology “UniCAR”
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Anja Feldmann1,*, Claudia Arndt1,*, Ralf Bergmann1,*, Simon Loff2,3,*, Marc Cartellieri1,4,*, Dominik Bachmann2,**, Roberta Aliperta1,**, Mirjam Hetzenecker2,**, Florian Ludwig2,**, Susann Albert2,**, Pauline Ziller-Walter2,**, Alexandra Kegler1,**, Stefanie Koristka1,**, Sebastian Gärtner1,**, Marc Schmitz5,7,8, Armin Ehninger3, Gerhard Ehninger2,6,7,8, Jens Pietzsch1,9, Jörg Steinbach1,7,8,9 and Michael Bachmann1,2,6,7,8
1Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Institute of Radiopharmaceutical Cancer Research, Dresden, Germany
2UniversityCancerCenter (UCC) ‘Carl Gustav Carus’ TU Dresden, Tumor Immunology, Dresden, Germany
3GEMoaB Monoclonals GmbH, Dresden, Germany
4Cellex Patient Treatment GmbH, Dresden, Germany
5Institute of Immunology, ‘Carl Gustav Carus’, TU Dresden, Dresden, Germany
6Medical Clinic and Policlinic I, University Hospital ‘Carl Gustav Carus’, TU Dresden, Dresden, Germany
7German Cancer Consortium (DKTK), partner site Dresden; and German Cancer Research Center (DKFZ), Heidelberg, Germany
8National Center for Tumor Diseases (NCT), Dresden, ‘Carl Gustav Carus’ TU Dresden, Dresden, Germany
9Department 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
Michael Bachmann, email: M.Bachmann@hzdr.de
Keywords: CAR, retargeting, T cells
Received: September 02, 2016 Accepted: January 04, 2017 Published: February 21, 2017
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.
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