Antibody-drug conjugates: the paradigm shifts in the targeted cancer therapy

Frontiers in Immunology

Immunology

Saad Mustafa¹  Md. Abdus Salam²  Sagnik Sengupta³  Devesh Aggarwal³  Md. Yusuf Al-Amin⁴  Jogendra Singh Pawar⁵  Jie Yang⁶  Mohammad Aasif Khan⁷  Xun Huang⁸ 

[1] Deen Dayal Upadhyaya (DDU) Kaushal Kendra, Jamia Millia Islamia University, New Delhi, India;Department of Basic Medical Sciences, Kulliyyah of Medicine, International Islamic University Malaysia, Kuantan, Malaysia;Department of Chemistry, Purdue University, West Lafayette, IN, United States;Department of Chemistry, Purdue University, West Lafayette, IN, United States;Purdue University Interdisciplinary Life Sciences Graduate Program, Purdue University, West Lafayette, IN, United States;Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, IN, United States;The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, Columbus, OH, United States;Department of Orthopedic Surgery, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China;Division of Hematology and Medical Oncology, Department of Medicine, University of Texas Health Science Center at San Antonio (UTHSCSA), San Antonio, TX, United States;Shandong Provincial Key Laboratory of Detection Technology for Tumor Markers, College of Medicine, Linyi University, Linyi, Shandong, China;

关键词: Antibody-drug conjugate (ADC);    targeted therapy;    cancer chemotherapy;    payloads;    warheads;   

DOI  :  10.3389/fimmu.2023.1203073

 received in 2023-04-10, accepted in 2023-07-27,  发布年份 2023

来源: Frontiers

【 摘 要 】

Cancer is one of the deadliest diseases, causing million of deaths each year globally. Conventional anti-cancer therapies are non-targeted and have systemic toxicities limiting their versatile applications in many cancers. So, there is an unmet need for more specific therapeutic options that will be effective as well as free from toxicities. Antibody-drug conjugates (ADCs) are suitable alternatives with the right potential and improved therapeutic index for cancer therapy. The ADCs are highly precise new class of biopharmaceutical products that covalently linked a monoclonal antibody (mAb) (binds explicitly to a tumor-associated surface antigen) with a customized cytotoxic drug (kills cancer cells) and tied via a chemical linker (releases the drug). Due to its precise design, it brings about the target cell killing sparing the normal counterpart and free from the toxicities of conventional chemotherapy. It has never been so easy to develop potential ADCs for successful therapeutic usage. With relentless efforts, it took almost a century for scientists to advance the formula and design ADCs for its current clinical applications. Until now, several ADCs have passed successfully through preclinical and clinical trials and because of proven efficacy, a few are approved by the FDA to treat various cancer types. Even though ADCs posed some shortcomings like adverse effects and resistance at various stages of development, with continuous efforts most of these limitations are addressed and overcome to improve their efficacy. In this review, the basics of ADCs, physical and chemical properties, the evolution of design, limitations, and future potentials are discussed.

【 授权许可】

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Copyright © 2023 Aggarwal, Yang, Salam, Sengupta, Al-Amin, Mustafa, Khan, Huang and Pawar