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Intracellular trafficking of new anticancer therapeutics: antibody–drug conjugates

Authors Kalim M, Chen J, Wang S, Lin C, Ullah S, Liang K, Ding Q, Chen S, Zhan JB

Received 24 February 2017

Accepted for publication 31 May 2017

Published 2 August 2017 Volume 2017:11 Pages 2265—2276

DOI https://doi.org/10.2147/DDDT.S135571

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Ashok Kumar Pandurangan

Peer reviewer comments 3

Editor who approved publication: Professor Manfred Ogris

Muhammad Kalim,1 Jie Chen,1 Shenghao Wang,1 Caiyao Lin,1 Saif Ullah,1 Keying Liang,1 Qian Ding,1 Shuqing Chen,2 Jinbiao Zhan1

1Department of Biochemistry and Genetics, School of Medicine, 2Department of Pharmaceutical Analysis, College of Pharmaceutical Science, Zhejiang University, Hangzhou, People’s Republic of China

Abstract: Antibody–drug conjugate (ADC) is a milestone in targeted cancer therapy that comprises of monoclonal antibodies chemically linked to cytotoxic drugs. Internalization of ADC takes place via clathrin-mediated endocytosis, caveolae-mediated endocytosis, and pinocytosis. Conjugation strategies, endocytosis and intracellular trafficking optimization, linkers, and drugs chemistry present a great challenge for researchers to eradicate tumor cells successfully. This inventiveness of endocytosis and intracellular trafficking has given consi­derable momentum recently to develop specific antibodies and ADCs to treat cancer cells. It is significantly advantageous to emphasize the endocytosis and intracellular trafficking pathways efficiently and to design potent engineered conjugates and biological entities to boost efficient therapies enormously for cancer treatment. Current studies illustrate endocytosis and intracellular trafficking of ADC, protein, and linker strategies in unloading and also concisely evaluate practically applicable ADCs.

Keywords: antibody–drug conjugate, antibody, endocytosis, intracellular trafficking, clathrin

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