A novel humanized anti-HER2 antibody conjugated with MMAE exerts potent anti-tumor activity
文献类型：期刊论文
| 作者 | Yao, Xuejing2; Jiang, Jing3; Wang, Xin2 ; Huang, Changjiang4; Li, Dong2; Xie, Kuan2; Xu, Qiaoyu4; Li, Hongwen2; Li, Zhuanglin4; Lou, Liguang5
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| 刊名 | BREAST CANCER RESEARCH AND TREATMENT
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| 出版日期 | 2015-08 |
| 卷号 | 153期号:1页码:123-133 |
| 关键词 | HER2 Antibody-drug conjugates Antibody therapy Tumor models MMAE |
| ISSN号 | 0167-6806 |
| DOI | 10.1007/s10549-015-3503-3 |
| 文献子类 | Article |
| 英文摘要 | Human epidermal growth factor receptor-2 (HER2) is a validated therapeutic target for breast cancer and trastuzumab (Herceptin), a humanized anti-HER2 antibody, has significant anti-cancer effects in the clinic. However, breast cancer patients often experience disease progression after prolonged Herceptin treatment. To develop a more effective therapy, we generated humanized monoclonal antibody hertuzumab and hertuzumab-drug conjugates as novel breast cancer therapies. The hertuzumab was conjugated with small molecule cytotoxic agents monomethylauristatin E (MMAE) or monomethylauristatin F (MMAF) with various linkers to generate antibody-drug conjugates (ADCs), which were evaluated for their in vitro and in vivo anti-cancer activities. Among these ADCs, hertuzumab-vc-MMAE can be effectively internalized and potently kill HER2 over-expressing tumor cells. In xenograft tumor models, hertuzumab-vc-MMAE showed a more potent anti-tumor activity than T-DM1, a FDA-approved ADC drug. More importantly, this novel ADC drug also showed superior anti-tumor activity than T-DM1 in trastuzumab- and lapatinib-resistant xenograft tumor models, suggesting its potential as an improved therapy for HER2-positive breast cancers. The novel ADC, hertuzumab-vc-MMAE, is an effective and selective agent for the treatment of HER2-positive breast tumors. |
| WOS关键词 | SENSITIVE DIPEPTIDE PRODRUGS ; HER2-POSITIVE BREAST-CANCER ; MONOCLONAL-ANTIBODY ; DRUG CONJUGATE ; GEMTUZUMAB OZOGAMICIN ; TRASTUZUMAB EMTANSINE ; PEPTIDE LINKERS ; CALICHEAMICIN ; CHEMOTHERAPY ; DOXORUBICIN |
| 资助项目 | National Science and Technology Major Project of China[2014ZX09508004001] |
| WOS研究方向 | Oncology |
| 语种 | 英语 |
| WOS记录号 | WOS:000359775100012 |
| 出版者 | SPRINGER |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/276448]  |
| 专题 | 药理学第一研究室 |
| 通讯作者 | Fang, Jianmin |
| 作者单位 | 1.Tongji Univ, Suzhou Inst, Suzhou 215101, Jiangsu, Peoples R China; 2.Tongji Univ, Sch Life Sci & Technol, Shanghai 200092, Peoples R China; 3.Binzhou Med Univ, Sch Pharm, Yantai 264005, Shandong, Peoples R China; 4.RemeGen Ltd, Yantai 264006, Shandong, Peoples R China; 5.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China; 6.Sichuan Univ, West China Hosp, Collaborat Innovat Ctr Biotherapy, Chengdu 610041, Peoples R China |
| 推荐引用方式 GB/T 7714 | Yao, Xuejing,Jiang, Jing,Wang, Xin,et al. A novel humanized anti-HER2 antibody conjugated with MMAE exerts potent anti-tumor activity[J]. BREAST CANCER RESEARCH AND TREATMENT,2015,153(1):123-133. |
| APA | Yao, Xuejing.,Jiang, Jing.,Wang, Xin.,Huang, Changjiang.,Li, Dong.,...&Fang, Jianmin.(2015).A novel humanized anti-HER2 antibody conjugated with MMAE exerts potent anti-tumor activity.BREAST CANCER RESEARCH AND TREATMENT,153(1),123-133. |
| MLA | Yao, Xuejing,et al."A novel humanized anti-HER2 antibody conjugated with MMAE exerts potent anti-tumor activity".BREAST CANCER RESEARCH AND TREATMENT 153.1(2015):123-133. |
入库方式： OAI收割
来源：上海药物研究所
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