机构：[1]School of Life Sciences and Technology, Tongji University , Shanghai , China.[2]RemeGen, Ltd. , Yantai , Shandong , China.[3]School of Pharmacy, Binzhou Medical University , Yantai , Shandong , China.[4]Shanghai Institute of Materia Medica, Chinese Academy of Sciences , Shanghai , China.[5]Tongji University Suzhou Institute , Suzhou , Jiangsu , China.[6]Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University , Chengdu , Sichuan , China.四川大学华西医院
Antibody-drug conjugate (ADC) is a novel class of therapeutics for cancer target therapy. This study assessed antitumor activity of ADC with an antimitotic agent, monomethyl auristatin E (MMAE) and a humanized monoclonal anti-HER2 antibody, hertuzumab, in gastric cancer. The efficacy of hertuzumab-MC-Val-Cit-PAB-MMAE (hertuzumab-vcMMAE) on human epidermal growth factor receptor 2 (HER2) positive human gastric cancer cells, NCI-N87, was evaluated in vitro and in vivo. The cytotoxicity of hertuzumab was significantly enhanced after conjugation with MMAE. Compared to trastuzumab, hertuzumab had a higher affinity to HER2 and had more potent antibody-dependent cell-mediated cytotoxicity (ADCC) activity in vitro. After conjugation with MMAE, the binding specificity for HER2 was not affected. Furthermore, the internalization of hertuzumab-vcMMAE in HER2 positive gastric cancer cells was verified. Although the conjugation of hertuzumab and MMAE decreased the ADCC effect, the overall cytotoxicity was dramatically increased in HER2 positive gastric cancer cells. In vitro data on this hertuzumab-vcMMAE has exerted much stronger antitumor activity compared to trastuzumab-DM1 in HER2 positive gastric cancer cells. A single administration of hertuzumab-vcMMAE at 5 or 10 mg/kg showed high potency and a sustained tumor inhibitory effect on NCI-N87 xenografts in mice. In conclusion, hertuzumab-vcMMAE conjugate is a highly effective anti-HER2 targeted therapy for HER2-positive gastric cancer.
基金：
This work was supported in part by grants from National Science and
Technology Major Project of China (#2014ZX09508004001 and
#2013ZX09401002), National Basic Research of China 973 program
(#2015cb553706), and National Natural Science Foundation of China
(#31270987).
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2016]版：
大类|3 区医学
小类|3 区肿瘤学
最新[2023]版：
大类|4 区医学
小类|4 区肿瘤学
第一作者：
第一作者机构：[1]School of Life Sciences and Technology, Tongji University , Shanghai , China.
通讯作者：
通讯机构：[1]School of Life Sciences and Technology, Tongji University , Shanghai , China.[5]Tongji University Suzhou Institute , Suzhou , Jiangsu , China.[6]Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University , Chengdu , Sichuan , China.
推荐引用方式(GB/T 7714)：
Li Hongwen,Yu Chao,Jiang Jing,et al.An anti-HER2 antibody conjugated with monomethyl auristatin E is highly effective in HER2-positive human gastric cancer.[J].Cancer biology & therapy.2016,17(4):346-54.doi:10.1080/15384047.2016.1139248.
APA：
Li Hongwen,Yu Chao,Jiang Jing,Huang Changjiang,Yao Xuejing...&Fang Jianmin.(2016).An anti-HER2 antibody conjugated with monomethyl auristatin E is highly effective in HER2-positive human gastric cancer..Cancer biology & therapy,17,(4)
MLA：
Li Hongwen,et al."An anti-HER2 antibody conjugated with monomethyl auristatin E is highly effective in HER2-positive human gastric cancer.".Cancer biology & therapy 17..4(2016):346-54
