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The Dawn of a New Era: Targeting the “Undruggables” with Antibody-Based Therapeutics

Qian, Linghui, Lin, Xuefen, Gao, Xue, Khan, Rizwan Ullah, Liao, Jia-Yu, Du, Shubo, Ge, Jingyan, Zeng, Su, Yao, Shao Q.·2023·Chemical Reviews
DOI 10.1021/acs.chemrev.2c00915
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Abstract

The high selectivity and affinity of antibodies toward their antigens have made them a highly valuable tool in disease therapy, diagnosis, and basic research. A plethora of chemical and genetic approaches have been devised to make antibodies accessible to more "undruggable" targets and equipped with new functions of illustrating or regulating biological processes more precisely. In this Review, in addition to introducing how naked antibodies and various antibody conjugates (such as antibody-drug conjugates, antibody-oligonucleotide conjugates, antibody-enzyme conjugates, etc.) work in therapeutic applications, special attention has been paid to how chemistry tools have helped to optimize the therapeutic outcome (i.e., with enhanced efficacy and reduced side effects) or facilitate the multifunctionalization of antibodies, with a focus on emerging fields such as targeted protein degradation, real-time live-cell imaging, catalytic labeling or decaging with spatiotemporal control as well as the engagement of antibodies inside cells. With advances in modern chemistry and biotechnology, well-designed antibodies and their derivatives via size miniaturization or multifunctionalization together with efficient delivery systems have emerged, which have gradually improved our understanding of important biological processes and paved the way to pursue novel targets for potential treatments of various diseases.

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Metadata

Authors
Qian, L., Lin, X., Gao, X., Khan, R. U., Liao, J.-Y., Du, S., Ge, J., Zeng, S., & Yao, S. Q.
Venue
Chemical Reviews
Publisher
American Chemical Society (ACS)
Published
2023-05-15
Volume
123
Issue
12
Pages
7782-7853
ISSN
  • 0009-2665
  • 1520-6890
DOI
10.1021/acs.chemrev.2c00915
Cited by
155
References
39
Language
en
Licence
Funders
  • Ministry of Education - Singapore (MOE T1: 22-5025-A0001, T2EP10222- 0002)
  • National Research Foundation Singapore (SBP-P4, SBP-P8)
  • National Natural Science Foundation of China (22177104, 81903574, 82273887)
  • Natural Science Foundation of Zhejiang Province (LTZ22B020001)

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