A novel humanized anti-HER2 antibody conjugated with MMAE exerts potent anti-tumor activity

doi:10.1007/s10549-015-3503-3

CORC > 上海药物研究所 > 中国科学院上海药物研究所 > 药理学第一研究室

	A novel humanized anti-HER2 antibody conjugated with MMAE exerts potent anti-tumor activity
	Yao, Xuejing 2; Jiang, Jing 3; Wang, Xin2 ; Huang, Changjiang 4; Li, Dong 2; Xie, Kuan 2; Xu, Qiaoyu 4; Li, Hongwen 2; Li, Zhuanglin 4; Lou, Liguang5
刊名	BREAST CANCER RESEARCH AND TREATMENT
	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.
资助项目	National Science and Technology Major Project of China[2014ZX09508004001]
WOS关键词	SENSITIVE DIPEPTIDE PRODRUGS ; HER2-POSITIVE BREAST-CANCER ; MONOCLONAL-ANTIBODY ; DRUG CONJUGATE ; GEMTUZUMAB OZOGAMICIN ; TRASTUZUMAB EMTANSINE ; PEPTIDE LINKERS ; CALICHEAMICIN ; CHEMOTHERAPY ; DOXORUBICIN
WOS研究方向	Oncology
语种	英语
出版者	SPRINGER
WOS记录号	WOS:000359775100012
内容类型	期刊论文
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.