Targeting pancreatic and ovarian carcinomas using the auristatin-based anti-CD70 antibody-drug conjugate SGN-75

Br J Cancer. 2010 Aug 24;103(5):676-84. doi: 10.1038/sj.bjc.6605816. Epub 2010 Jul 27.


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.

Conclusion: 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.

MeSH terms

  • Aminobenzoates / administration & dosage*
  • Animals
  • Antibodies, Monoclonal / therapeutic use
  • CD27 Ligand / immunology*
  • Cell Line, Tumor
  • Drug Delivery Systems
  • Drug Screening Assays, Antitumor
  • Female
  • Humans
  • Immunoconjugates / therapeutic use*
  • Mice
  • Mice, Nude
  • Oligopeptides / administration & dosage*
  • Ovarian Neoplasms / therapy*
  • Pancreatic Neoplasms / therapy*


  • Aminobenzoates
  • Antibodies, Monoclonal
  • CD27 Ligand
  • Immunoconjugates
  • Oligopeptides
  • auristatin