Abstract #4652: CD70 expression in multiple types of carcinomas: new targets for auristatin-based anti-CD70 antibody-drug conjugate, SGN-75

CD70, a transmembrane type II protein, is a member of the tumor necrosis factor (TNF) family. CD70 has been previously reported to be highly expressed in solid tumors (renal cell and nasopharyngeal carcinomas) as well as hematologic malignancies and has very limited expression in normal cells (activated lymphocytes, dendritic cells). An extensive expression profiling study for CD70 in carcinomas has been a challenge in the past due to a lack of an anti-CD70 reagent that works well in formalin-fixed paraffin embedded (FFPE) tissues. Murine monoclonal antibodies were generated and validated for specific CD70 staining and a protocol for immunohistochemical (IHC) analysis using FFPE samples was developed. Tissue microarray analysis of various types of tumors confirmed CD70 expression in kidney cancers (70% of cases). In addition, we report novel detection of significant CD70 expression in carcinomas such as pancreatic (25% of cases), larynx/pharynx (22%), ovarian (15%), skin (13%), lung (10%), and colon (9%). We also detected CD70 expression in tumor cell lines from the same indications by IHC and flow cytometric analyses. Using CD70+ ovarian and pancreatic cell lines, we show in vitro efficacy of our anti-CD70 antibody-drug conjugate, SGN-75. These results demonstrate the potential application of anti-CD70 ADCs for treatment of ovarian and pancreatic cancers. Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 4652.