癌症研究
免疫组织化学
浆液性液体
抗体
卵巢癌
生物
胰腺癌
体内
单克隆抗体
病理
癌症
医学
免疫学
遗传学
生物技术
作者
Ryan Mc,Heather Kostner,Gordon Ka,Steven Duniho,Sutherland Mk,Chen Yu,Kim Km,Albina Nesterova,Martha E. Anderson,McEarchern Ja,Law Cl,L.A. Smith
标识
DOI:10.1038/sj.bjc.6605816
摘要
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. 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. 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. 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.
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