title: Retargeting of T cells to prostate stem cell antigen expressing tumor cells: comparison of different antibody formats.
abstract: BACKGROUND
  Prostate cancer (PCa) is the most common malignant disease in men. Novel treatment options are needed for patients after development of metastatic, hormone-refractory disease or for those who have failed a local treatment. The prostate stem cell antigen (PSCA) is expressed in >80% of primary PCa samples and bone metastases. Its expression is increased both in androgen-dependent and independent prostate tumors, particularly in carcinomas of high stages and Gleason scores. Therefore, PSCA is an attractive target for immunotherapy of PCa by retargeting of T cells to tumor cells.
  
  
  METHODS
  A series of different bispecific antibody formats for retargeting of T cells to tumor cells were described but, only very limited data obtained by side by side comparison of the different antibody formats are available. We established two novel bispecific antibodies in different formats. The functionality of both constructs was analyzed by FACS and chromium release assays. In parallel, the release of pro-inflammatory cytokines was determined by ELISA.
  
  
  CONCLUSIONS
  Irrespective of the underlying antibody format, both novel bispecific antibodies cause an efficient killing of PSCA-positive tumor cells by pre- and non-pre-activated T cells. Killing and release of pro-inflammatory cytokines requires an antigen specific cross-linkage of the T cells with the target cells.
authors.affiliation: Medical Faculty Carl Gustav Carus, Institute of Immunology, Technical University Dresden, Dresden, Germany.
authors.forename: Anja
authors.initials: A
authors.lastname: Feldmann
authors.forename: Slava
authors.initials: S
authors.lastname: Stamova
authors.forename: Claudia C
authors.initials: CC
authors.lastname: Bippes
authors.forename: Holger
authors.initials: H
authors.lastname: Bartsch
authors.forename: Rebekka
authors.initials: R
authors.lastname: Wehner
authors.forename: Marc
authors.initials: M
authors.lastname: Schmitz
authors.forename: Achim
authors.initials: A
authors.lastname: Temme
authors.forename: Marc
authors.initials: M
authors.lastname: Cartellieri
authors.forename: Michael
authors.initials: M
authors.lastname: Bachmann
mesh_terms: D018033:Antibodies, Bispecific / Q000276:immunology / Q000494:pharmacology*; D000951:Antigens, Neoplasm / Q000276:immunology*; D045744:Cell Line, Tumor; D016207:Cytokines / Q000032:analysis; D003601:Cytotoxicity Tests, Immunologic; D005434:Flow Cytometry; D058851:GPI-Linked Proteins / Q000276:immunology; D006801:Humans; D007116:Immunization, Passive / Q000379:methods; D008297:Male; D009363:Neoplasm Proteins / Q000276:immunology*; D009376:Neoplasms, Hormone-Dependent / Q000276:immunology / Q000628:therapy; D011471:Prostatic Neoplasms / Q000276:immunology* / Q000628:therapy; D012313:RNA / Q000737:chemistry / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D018033:Antibodies, Bispecific; D000951:Antigens, Neoplasm; D016207:Cytokines; D058851:GPI-Linked Proteins; D009363:Neoplasm Proteins; C110843:PSCA protein, human; D012313:RNA