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.

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.

• Authors: M C Ryan, H Kostner, K A Gordon, S Duniho, M K Sutherland, C Yu, K M Kim, A Nesterova, M Anderson, J A McEarchern, C-L Law, L M Smith
• Journal: British journal of cancer (Br J Cancer) Vol. 103 Issue 5 Pg. 676-84 (Aug 24 2010) ISSN: 1532-1827 [Electronic] England
• PMID: 20664585 (Publication Type: Journal Article)

Chemical References

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

Topics

• 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)