shra1403anovelcmetantibodydrugconjugateexertsencouragingantitumoractivityincmetoverexpressingmodels

doi:10.1038/s41401-018-0198-0

	shra1403anovelcmetantibodydrugconjugateexertsencouragingantitumoractivityincmetoverexpressingmodels
	Yang Changyong 2; Wang Lei 3; Sun Xing 1; Tang Mi 1; Quan Haitian 3; Zhang Lianshan 1; Lou Liguang 3; Gou Shaohua 2
刊名	actapharmacologicasinica
	2019
卷号	40 期号:7 页码:971
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
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.
语种	英语
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/286464]
专题	中国科学院上海药物研究所
作者单位	1.Jiangsu Hengrui Medicine Co., Ltd 2.东南大学 3.中国科学院上海药物研究所
推荐引用方式 GB/T 7714	Yang Changyong,Wang Lei,Sun Xing,et al. shra1403anovelcmetantibodydrugconjugateexertsencouragingantitumoractivityincmetoverexpressingmodels[J]. actapharmacologicasinica,2019,40(7):971.
APA	Yang Changyong.,Wang Lei.,Sun Xing.,Tang Mi.,Quan Haitian.,...&Gou Shaohua.(2019).shra1403anovelcmetantibodydrugconjugateexertsencouragingantitumoractivityincmetoverexpressingmodels.actapharmacologicasinica,40(7),971.
MLA	Yang Changyong,et al."shra1403anovelcmetantibodydrugconjugateexertsencouragingantitumoractivityincmetoverexpressingmodels".actapharmacologicasinica 40.7(2019):971.