A novel humanized anti-HER2 antibody conjugated with MMAE exerts potent anti-tumor activity外文翻译.PDFVIP

Breast Cancer Res Treat DOI 10.1007/s10549-015-3503-3 PRECLINICAL STUDY A novel humanized anti-HER2 antibody conjugated with MMAE exerts potent anti-tumor activity 1 2 1 3 1 Xuejing Yao • Jing Jiang • Xin Wang • Changjiang Huang • Dong Li • 1 3 1 3 4 Kuan Xie • Qiaoyu Xu • Hongwen Li • Zhuanglin Li • Liguang Lou • Jianmin Fang1,5,6 Received: 10 June 2015 / Accepted: 15 July 2015 Springer Science+Business Media New York 2015 Abstract Human epidermal growth factor receptor-2 T-DM1 in trastuzumab- and lapatinib-resistant xenograft (HER2) is a validated therapeutic target for breast cancer tumor models, suggesting its potential as an improved and trastuzumab (Herceptin), a humanized anti-HER2 therapy for HER2-positive breast cancers. The novel ADC, antibody, has significant anti-cancer effects in the clinic. hertuzumab-vc-MMAE, is an effective and selective agent However, breast cancer patients often experience disease for the treatment of HER2-positive breast tumors. progression after prolonged Herceptin treatment. To develop a more effective therapy, we generated humanized Keywords HER2 Antibody–drug conjugates monoclonal antibody hertuzumab and hertuzumab-drug Antibody therapy Tumor models MMAE conjugates as novel breast cancer therapies. The her- tuzumab was conjugated with small molecule cytotoxic agents monomethylauristatin E (MMAE) or monomethy- Introduction lauristatin F (MMAF) with various linkers to generate antibody–drug conjugates (ADCs), which were evaluated Human epidermal growt