Seattle Genetics, Inc. 21823 - 30th Drive SE, Bothell, WA 98021, USA.
Br J Cancer. 2010 Aug 24;103(5):676-84. doi: 10.1038/sj.bjc.6605816. Epub 2010 Jul 27.
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.
CD70 在肾细胞癌和非霍奇金淋巴瘤中异常高表达，在正常组织中表达受限，因此是抗体治疗的理想靶点。由于缺乏在福尔马林固定石蜡包埋（FFPE）组织中有效的 CD70 特异性试剂，因此对 CD70 在癌中的表达谱进行分析受到限制。
我们生成了针对 CD70 的鼠单克隆抗体（mAb），并通过 Western blot 分析验证了其特异性，还开发了用于 FFPE 组织免疫组织化学的方案。使用 CD70+肿瘤细胞系测试了抗 CD70 抗体药物偶联物 SGN-75 的抗肿瘤活性。
我们报告了 CD70 在多种癌症中的新型表达检测，包括胰腺癌（25%）、喉/咽癌（22%）、黑色素瘤（16%）、卵巢癌（15%）、肺癌（10%）和结肠癌（9%）。我们的结果表明，表达高水平内源性或转染的 CD70 的胰腺和卵巢肿瘤细胞系在体外和体内对 SGN-75 的抗肿瘤活性敏感。
开发用于 FFPE 样本的稳健和广泛筛选的鼠 mAb，以及在新适应症中检测抗肿瘤活性，为 SGN-75 用于治疗多种表达 CD70 的癌症提供了依据。
