title: Retargeting of T lymphocytes to PSCA- or PSMA positive prostate cancer cells using the novel modular chimeric antigen receptor platform technology "UniCAR".
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.
authors.affiliation: Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Institute of Radiopharmaceutical Cancer Research, Dresden, Germany.
authors.forename: Anja
authors.initials: A
authors.lastname: Feldmann
authors.affiliation: Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Institute of Radiopharmaceutical Cancer Research, Dresden, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Arndt
authors.affiliation: Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Institute of Radiopharmaceutical Cancer Research, Dresden, Germany.
authors.forename: Ralf
authors.initials: R
authors.lastname: Bergmann
authors.affiliation: UniversityCancerCenter (UCC) 'Carl Gustav Carus' TU Dresden, Tumor Immunology, Dresden, Germany.|GEMoaB Monoclonals GmbH, Dresden, Germany.
authors.forename: Simon
authors.initials: S
authors.lastname: Loff
authors.affiliation: Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Institute of Radiopharmaceutical Cancer Research, Dresden, Germany.|Cellex Patient Treatment GmbH, Dresden, Germany.
authors.forename: Marc
authors.initials: M
authors.lastname: Cartellieri
authors.affiliation: UniversityCancerCenter (UCC) 'Carl Gustav Carus' TU Dresden, Tumor Immunology, Dresden, Germany.
authors.forename: Dominik
authors.initials: D
authors.lastname: Bachmann
authors.affiliation: Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Institute of Radiopharmaceutical Cancer Research, Dresden, Germany.
authors.forename: Roberta
authors.initials: R
authors.lastname: Aliperta
authors.affiliation: UniversityCancerCenter (UCC) 'Carl Gustav Carus' TU Dresden, Tumor Immunology, Dresden, Germany.
authors.forename: Mirjam
authors.initials: M
authors.lastname: Hetzenecker
authors.affiliation: UniversityCancerCenter (UCC) 'Carl Gustav Carus' TU Dresden, Tumor Immunology, Dresden, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Ludwig
authors.affiliation: UniversityCancerCenter (UCC) 'Carl Gustav Carus' TU Dresden, Tumor Immunology, Dresden, Germany.
authors.forename: Susann
authors.initials: S
authors.lastname: Albert
authors.affiliation: UniversityCancerCenter (UCC) 'Carl Gustav Carus' TU Dresden, Tumor Immunology, Dresden, Germany.
authors.forename: Pauline
authors.initials: P
authors.lastname: Ziller-Walter
authors.affiliation: Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Institute of Radiopharmaceutical Cancer Research, Dresden, Germany.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Kegler
authors.affiliation: Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Institute of Radiopharmaceutical Cancer Research, Dresden, Germany.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Koristka
authors.affiliation: Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Institute of Radiopharmaceutical Cancer Research, Dresden, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Gärtner
authors.affiliation: 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.
authors.forename: Marc
authors.initials: M
authors.lastname: Schmitz
authors.affiliation: GEMoaB Monoclonals GmbH, Dresden, Germany.
authors.forename: Armin
authors.initials: A
authors.lastname: Ehninger
authors.affiliation: 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.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Ehninger
authors.affiliation: 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.
authors.forename: Jens
authors.initials: J
authors.lastname: Pietzsch
authors.affiliation: 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.
authors.forename: Jörg
authors.initials: J
authors.lastname: Steinbach
authors.affiliation: 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.
authors.forename: Michael
authors.initials: M
authors.lastname: Bachmann
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology* / Q000378:metabolism*; D045744:Cell Line, Tumor; D016207:Cytokines / Q000378:metabolism; D003602:Cytotoxicity, Immunologic; D004195:Disease Models, Animal; D058851:GPI-Linked Proteins / Q000276:immunology / Q000378:metabolism; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D007167:Immunotherapy; D007963:Leukocytes, Mononuclear; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D051379:Mice; D009363:Neoplasm Proteins / Q000276:immunology* / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000235:genetics / Q000276:immunology* / Q000378:metabolism* / Q000628:therapy; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins; D037182:T-Cell Antigen Receptor Specificity / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000951:Antigens, Neoplasm; D016207:Cytokines; D058851:GPI-Linked Proteins; D009363:Neoplasm Proteins; C110843:PSCA protein, human; D011948:Receptors, Antigen, T-Cell; D011993:Recombinant Fusion Proteins
keywords: CAR; T cells; retargeting