Antibody drug conjugate: the "biological missile" for targeted cancer therapy

Signal Transduct Target Ther. 2022 Mar 22;7(1):93. doi: 10.1038/s41392-022-00947-7.

Zhiwen Fu ¹ ², Shijun Li ¹ ², Sifei Han ³ ⁴, Chen Shi ⁵ ⁶, Yu Zhang ⁷ ⁸

Affiliations

1 Department of Pharmacy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People's Republic of China.
2 Hubei Province Clinical Research Center for Precision Medicine for Critical Illness, Wuhan, 430022, People's Republic of China.
3 Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, (Parkville Campus) 381 Royal Parade,, Parkville, VIC, 3052, Australia.
4 Faculty of Pharmacy, China Pharmaceutical University, 639 Longmian Avenue, Jiangning District, Nanjing, 211198, People's Republic of China.
5 Department of Pharmacy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People's Republic of China. [email protected].
6 Hubei Province Clinical Research Center for Precision Medicine for Critical Illness, Wuhan, 430022, People's Republic of China. [email protected].
7 Department of Pharmacy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People's Republic of China. [email protected].
8 Hubei Province Clinical Research Center for Precision Medicine for Critical Illness, Wuhan, 430022, People's Republic of China. [email protected].

PMID: 35318309 DOI: 10.1038/s41392-022-00947-7

Abstract

Antibody-drug conjugate (ADC) is typically composed of a monoclonal antibody (mAbs) covalently attached to a cytotoxic drug via a chemical linker. It combines both the advantages of highly specific targeting ability and highly potent killing effect to achieve accurate and efficient elimination of Cancer cells, which has become one of the hotspots for the research and development of Anticancer drugs. Since the first ADC, Mylotarg^® (gemtuzumab ozogamicin), was approved in 2000 by the US Food and Drug Administration (FDA), there have been 14 ADCs received market approval so far worldwide. Moreover, over 100 ADC candidates have been investigated in clinical stages at present. This kind of new anti-cancer drugs, known as "biological missiles", is leading a new era of targeted Cancer therapy. Herein, we conducted a review of the history and general mechanism of action of ADCs, and then briefly discussed the molecular aspects of key components of ADCs and the mechanisms by which these key factors influence the activities of ADCs. Moreover, we also reviewed the approved ADCs and Other promising candidates in phase-3 clinical trials and discuss the current challenges and future perspectives for the development of next generations, which provide insights for the research and development of novel Cancer therapeutics using ADCs.

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