SHR-A1403, a novel c-Met antibody-drug conjugate, exerts encouraging anti-tumor activity in c-Met-overexpressing models

doi:10.1038/s41401-018-0198-0

	SHR-A1403, a novel c-Met antibody-drug conjugate, exerts encouraging anti-tumor activity in c-Met-overexpressing models
	Yang, Chang-yong 1,2,3,4; Wang, Lei 5; Sun, Xing 4; Tang, Mi 4; Quan, Hai-tian 5; Zhang, Lian-shan 4; Lou, Li-guang 5; Gou, Shao-hua 1,2,3
刊名	ACTA PHARMACOLOGICA SINICA
	2019-07-01
卷号	40 期号:7 页码:971-979
关键词	SHR-A1403 c-Met ADC anti-tumor patient-derived xenograft (PDX) molecular mechanisms
ISSN号	1671-4083
DOI	10.1038/s41401-018-0198-0
通讯作者	Gou, Shao-hua(sgou@seu.edu.cn)
英文摘要	Emerging evidence demonstrates that a c-Met antibody-drug conjugate (ADC) has superior efficacy and safety profiles compared with those of currently available small molecules or antibody inhibitors for the treatment of c-Met-overexpressing cancers. Here we described both the in vitro and in vivo efficacies of SHR-A1403, a novel c-Met ADC composed of a humanized IgG2 monoclonal antibody against c-Met conjugated to a novel cytotoxic microtubule inhibitor. SHR-A1403 showed high affinity to c-Met proteins derived from human or monkey and potent inhibitory effects in cancer cell lines with high c-Met protein expression. In mice bearing tumors derived from cancer cell lines or patient HCC tissues with confirmed c-Met overexpression, SHR-A1403 showed excellent anti-tumor efficacy. Antibody binding with c-Met contributed to SHR-A1403 endocytosis; the subsequent translocation to lysosomes and cytotoxicity of the released toxin are speculated to be predominant mechanisms underlying the anti-tumor activity of SHR-A1403. In conclusion, SHR-A1403 showed significant anti-tumor activity in cancer cell lines, xenograft mouse models and an HCC PDX model, which all have high c-Met levels. These data provide references for SHR-A1403 as a potential therapy for the treatment of cancers with c-Met overexpression.
WOS关键词	TYROSINE KINASE ; HGF RECEPTOR ; PHASE-I ; CANCER ; GROWTH ; TRAFFICKING ; INHIBITORS ; DISCOVERY ; TARGET ; TUMORS
WOS研究方向	Chemistry ; Pharmacology & Pharmacy
语种	英语
出版者	NATURE PUBLISHING GROUP
WOS记录号	WOS:000472610000011
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/289397]
专题	中国科学院上海药物研究所
通讯作者	Gou, Shao-hua
作者单位	1.Southeast Univ, Pharmaceut Res Ctr, Nanjing 211189, Jiangsu, Peoples R China 2.Southeast Univ, Sch Chem & Chem Engn, Nanjing 211189, Jiangsu, Peoples R China 3.Southeast Univ, Jiangsu Prov Hitech Key Lab Biomed Res, Nanjing 211189, Jiangsu, Peoples R China 4.Jiangsu Hengrui Med Co Ltd, Lianyungang 222047, Peoples R China 5.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China
推荐引用方式 GB/T 7714	Yang, Chang-yong,Wang, Lei,Sun, Xing,et al. SHR-A1403, a novel c-Met antibody-drug conjugate, exerts encouraging anti-tumor activity in c-Met-overexpressing models[J]. ACTA PHARMACOLOGICA SINICA,2019,40(7):971-979.
APA	Yang, Chang-yong.,Wang, Lei.,Sun, Xing.,Tang, Mi.,Quan, Hai-tian.,...&Gou, Shao-hua.(2019).SHR-A1403, a novel c-Met antibody-drug conjugate, exerts encouraging anti-tumor activity in c-Met-overexpressing models.ACTA PHARMACOLOGICA SINICA,40(7),971-979.
MLA	Yang, Chang-yong,et al."SHR-A1403, a novel c-Met antibody-drug conjugate, exerts encouraging anti-tumor activity in c-Met-overexpressing models".ACTA PHARMACOLOGICA SINICA 40.7(2019):971-979.