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Spatiotemporal Quantification of HER2-targeting Antibody-Drug Conjugate Bystander Activity and Enhancement of Solid Tumor Penetration

文献类型：期刊论文

作者Wei, Qing9,10,11; Yang, Teng7,8; Zhu, Jiayu6; Zhang, Ziwen10; Yang, Le8,9; Zhang, Yuchao8; Hu, Can9,11; Chen, Jiahui9,11; Wang, Jinchao8; Tian, Xuefei4,5,8
刊名CLINICAL CANCER RESEARCH
出版日期2024-03-01
卷号30期号:5页码:984-997
ISSN号1078-0432
DOI10.1158/1078-0432.CCR-23-1725
通讯作者Ying, Jieer(chengxd@zjcc.org.cn) ; Fan, Mengyang(guopeng@ucas.ac.cn) ; Guo, Peng(fanmy@ibmc.ac.cn) ; Cheng, Xiangdong(jieerying@aliyun.com)
英文摘要Purpose: Antibody-drug conjugate (ADC) has had a transformative effect on the treatment of many solid tumors, yet it remains unclear how ADCs exert bystander activity in the tumor microenvironment.Experimental Design: Here, we directly visualized and spatiotemporally quantified the intratumor biodistribution and pharmacokinetics of different ADC components by developing dual-labeled fluorescent probes.Results: Mechanistically, we found that tumor penetration of ADCs is distinctly affected by their ability to breach the binding site barrier (BSB) in perivascular regions of tumor vasculature, and bystander activity of ADC can only partially breach BSB. Furthermore, bystander activity of ADCs can work in synergy with coadministration of their parental antibodies, leading to fully bypassing BSBs and enhancing tumor penetration via a two-step process.Conclusions: These promising preclinical data allowed us to initiate a phase I/II clinical study of coadministration of RC48 and trastuzumab in patients with malignant stomach cancer to further evaluate this treatment strategy in humans.
WOS关键词MONOCLONAL-ANTIBODIES ; TRASTUZUMAB DERUXTECAN ; DS-8201A ; MACROMOLECULES ; EMTANSINE ; EFFICACY ; ADC
资助项目National Natural Science Foundation of China (NSFC)[82074245] ; National Natural Science Foundation of China (NSFC)[82172598] ; National Natural Science Foundation of China (NSFC)[8237131606] ; National Natural Science Foundation of China (NSFC)[82303963] ; National Natural Science Foundation of China[2021YFA0910100] ; National Key Research and Development Program of China[LZ22H310001] ; National Key Research and Development Program of China[LQ21H160005] ; Natural Science Foundation of Zhejiang Province[2022ZDSJ0474] ; Agricultural and Social Development Research Project of Hangzhou Municipal Science and Technology Bureau[2022R01006] ; Zhejiang Leading Innovation and Entrepreneurship Team[2022E10021] ; Key Laboratory of Prevention, Diagnosis and Therapy of Upper Gastrointestinal Cancer of Zhejiang Province[JBZX-202006] ; Zhejiang Provincial Research Center for Upper Gastrointestinal Track Center ; Science Experiment Center at Hangzhou Institute of Medicine (HIM)
WOS研究方向Oncology
语种英语
WOS记录号WOS:001178765600012
出版者AMER ASSOC CANCER RESEARCH
源URL[http://119.78.100.183/handle/2S10ELR8/310348]  
专题中国科学院上海药物研究所
通讯作者Ying, Jieer; Fan, Mengyang; Guo, Peng; Cheng, Xiangdong
作者单位1.Zhejiang Canc Hosp, Hangzhou 310022, Peoples R China
2.Tongji Univ, Sch Life Sci & Technol, Shanghai, Peoples R China
3.Nagoya City Univ, Grad Sch Med Sci, Dept Gastroenterol & Metab, Nagoya, Japan
4.Univ Chinese Acad Sci, Hangzhou Inst Adv Study HIAS, Coll Mol Med, Hangzhou, Peoples R China
5.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai, Peoples R China
6.Zhejiang Chinese Med Univ, Hangzhou, Peoples R China
7.Zhejiang Univ Technol, Coll Pharmaceut Sci, Hangzhou, Peoples R China
8.Chinese Acad Sci, Hangzhou Inst Med HIM, Hangzhou, Peoples R China
9.Upper Gastrointestinal Canc Zhejiang Prov, Key Lab Prevent Diag & Therapy, Hangzhou, Peoples R China
10.Zhejiang Canc Hosp, Dept Med Oncol, Hangzhou, Peoples R China
推荐引用方式
GB/T 7714		 Wei, Qing,Yang, Teng,Zhu, Jiayu,et al. Spatiotemporal Quantification of HER2-targeting Antibody-Drug Conjugate Bystander Activity and Enhancement of Solid Tumor Penetration[J]. CLINICAL CANCER RESEARCH,2024,30(5):984-997.
APA Wei, Qing.,Yang, Teng.,Zhu, Jiayu.,Zhang, Ziwen.,Yang, Le.,...&Cheng, Xiangdong.(2024).Spatiotemporal Quantification of HER2-targeting Antibody-Drug Conjugate Bystander Activity and Enhancement of Solid Tumor Penetration.CLINICAL CANCER RESEARCH,30(5),984-997.
MLA Wei, Qing,et al."Spatiotemporal Quantification of HER2-targeting Antibody-Drug Conjugate Bystander Activity and Enhancement of Solid Tumor Penetration".CLINICAL CANCER RESEARCH 30.5(2024):984-997.

入库方式： OAI收割

来源：上海药物研究所

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