title: Targeting pancreatic and ovarian carcinomas using the auristatin-based anti-CD70 antibody-drug conjugate SGN-75.
abstract: BACKGROUND
  CD70 is an ideal target for antibody-based therapies because of its aberrant high expression in renal carcinomas and non-Hodgkin lymphomas and its highly restricted expression in normal tissues. The expression profiling of CD70 in carcinomas has been limited because of the lack of a CD70-specific reagent that works in formalin-fixed paraffin-embedded (FFPE) tissues.
  
  
  METHODS
  We generated murine monoclonal antibodies (mAbs) specific for CD70 and validated their specificity by western blot analysis and developed a protocol for immunohistochemistry on FFPE tissues. CD70+ tumour cell lines were used for testing the anti-tumour activity of the anti-CD70 antibody-drug conjugate, SGN-75.
  
  
  RESULTS
  We report novel detection of CD70 expression in multiple cancers including pancreatic (25%), larynx/pharynx (22%), melanoma (16%), ovarian (15%), lung (10%), and colon (9%). Our results show that pancreatic and ovarian tumour cell lines, which express high levels of endogenous or transfected CD70, are sensitive to the anti-tumour activity of SGN-75 in vitro and in vivo.
  
  
  CONCLUSIONS
  Development of murine mAbs for robust and extensive screening of FFPE samples coupled with the detection of anti-tumour activity in novel indications provide rationale for expanding the application of SGN-75 for the treatment of multiple CD70 expressing cancers.
authors.affiliation: Seattle Genetics, Inc. 21823 - 30th Drive SE, Bothell, WA 98021, USA.
authors.forename: M C
authors.initials: MC
authors.lastname: Ryan
authors.forename: H
authors.initials: H
authors.lastname: Kostner
authors.forename: K A
authors.initials: KA
authors.lastname: Gordon
authors.forename: S
authors.initials: S
authors.lastname: Duniho
authors.forename: M K
authors.initials: MK
authors.lastname: Sutherland
authors.forename: C
authors.initials: C
authors.lastname: Yu
authors.forename: K M
authors.initials: KM
authors.lastname: Kim
authors.forename: A
authors.initials: A
authors.lastname: Nesterova
authors.forename: M
authors.initials: M
authors.lastname: Anderson
authors.forename: J A
authors.initials: JA
authors.lastname: McEarchern
authors.forename: C-L
authors.initials: CL
authors.lastname: Law
authors.forename: L M
authors.initials: LM
authors.lastname: Smith
mesh_terms: D062365:Aminobenzoates / Q000008:administration & dosage*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D053282:CD27 Ligand / Q000276:immunology*; D045744:Cell Line, Tumor; D016503:Drug Delivery Systems; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D018796:Immunoconjugates / Q000627:therapeutic use*; D051379:Mice; D008819:Mice, Nude; D009842:Oligopeptides / Q000008:administration & dosage*; D010051:Ovarian Neoplasms / Q000628:therapy*; D010190:Pancreatic Neoplasms / Q000628:therapy*
chemical_list: D062365:Aminobenzoates; D000911:Antibodies, Monoclonal; D053282:CD27 Ligand; D018796:Immunoconjugates; D009842:Oligopeptides; C543533:auristatin