title: Targeting of tumor cells expressing the prostate stem cell antigen (PSCA) using genetically engineered T-cells.
abstract: BACKGROUND
  Curative therapeutic options for minimal residual disease or advanced tumor stages in prostate cancer (PCa) are still missing. Adoptive transfer of cytotoxic T-cells that have been polyclonally rendered tumor-specific by genetic engineering appears to be a promising immunotherapeutic strategy. Among the numerous prostate tissue/tumor antigens identified during the last years, the "prostate stem cell antigen" (PSCA) is an attractive immunotherapeutic target. It is broadly expressed on the surface of primary PCa cells as well as on PCa metastases.
  
  
  METHODS
  To generate a chimeric T-cell receptor (TCR) recognizing PSCA, a monoclonal anti-PSCA antibody was raised and a single-chain fragment (scFv) was prepared. The resulting anti-PSCA scFv 7F5 was fused to the beta2 constant region derived from the beta-chain of a TCR and to the CD3zeta-signaling domain.
  
  
  RESULTS
  The chimeric alpha-PSCA-beta2/CD3zeta-TCR, expressed in Jurkat cells, was phosphorylated in the ITAMs of the CD3-zeta chain upon cross-linking by insolublized PSCA. When transduced into a mouse cytotoxic T-cell line, the chimeric receptor specifically activated cytotoxicity against PSCA-positive tumor cells.
  
  
  CONCLUSIONS
  We developed a functional chimeric TCR against PSCA for treatment of PCa. The chimeric alpha-PSCA-beta2/CD3zeta-TCR might now be used for arming human cytotoxic T-cells for further studies towards a clinical treatment of PCa.
authors.affiliation: Institute of Immunology, Medical Faculty Carl Gustav Carus, Technical University Dresden, Dresden, Germany.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Morgenroth
authors.forename: Marc
authors.initials: M
authors.lastname: Cartellieri
authors.forename: Marc
authors.initials: M
authors.lastname: Schmitz
authors.forename: Serap
authors.initials: S
authors.lastname: Günes
authors.forename: Bernd
authors.initials: B
authors.lastname: Weigle
authors.forename: Michael
authors.initials: M
authors.lastname: Bachmann
authors.forename: Hinrich
authors.initials: H
authors.lastname: Abken
authors.forename: Ernst Peter
authors.initials: EP
authors.lastname: Rieber
authors.forename: Achim
authors.initials: A
authors.lastname: Temme
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000378:metabolism; D000951:Antigens, Neoplasm; D002460:Cell Line; D045744:Cell Line, Tumor; D002678:Chimera / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D058851:GPI-Linked Proteins; D005818:Genetic Engineering; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D019169:Jurkat Cells; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D009363:Neoplasm Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000276:immunology / Q000378:metabolism* / Q000628:therapy; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology / Q000378:metabolism* / Q000473:pathology; D014162:Transfection
chemical_list: D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D058851:GPI-Linked Proteins; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; C110843:PSCA protein, human; D011948:Receptors, Antigen, T-Cell