Antibody–drug conjugates: Recent advances in linker chemistry
Antibody–drug conjugates (ADCs) are gradually revolutionizing clinical cancer therapy. The antibody–drug conjugate linker molecule determines both the efficacy and the adverse effects, and so has a major influence on the fate of ADCs. An ideal linker should be stable in the circulatory system and re...
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| Published in | Acta pharmaceutica Sinica. B Vol. 11; no. 12; pp. 3889 - 3907 |
|---|---|
| Main Authors | , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
Netherlands
Elsevier B.V
01.12.2021
Elsevier |
| Subjects | |
| Online Access | Get full text |
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| Abstract | Antibody–drug conjugates (ADCs) are gradually revolutionizing clinical cancer therapy. The antibody–drug conjugate linker molecule determines both the efficacy and the adverse effects, and so has a major influence on the fate of ADCs. An ideal linker should be stable in the circulatory system and release the cytotoxic payload specifically in the tumor. However, existing linkers often release payloads nonspecifically and inevitably lead to off-target toxicity. This defect is becoming an increasingly important factor that restricts the development of ADCs. The pursuit of ADCs with optimal therapeutic windows has resulted in remarkable progress in the discovery and development of novel linkers. The present review summarizes the advance of the chemical trigger, linker‒antibody attachment and linker‒payload attachment over the last 5 years, and describes the ADMET properties of ADCs. This work also helps clarify future developmental directions for the linkers.
Antibody–drug conjugates (ADCs) are revolutionizing cancer therapy. Linkers, determining both efficacy and off-target toxicity, are the core components of ADCs. The advances of linkers over the past 5 years are reviewed. [Display omitted] |
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| AbstractList | Antibody–drug conjugates (ADCs) are gradually revolutionizing clinical cancer therapy. The antibody–drug conjugate linker molecule determines both the efficacy and the adverse effects, and so has a major influence on the fate of ADCs. An ideal linker should be stable in the circulatory system and release the cytotoxic payload specifically in the tumor. However, existing linkers often release payloads nonspecifically and inevitably lead to off-target toxicity. This defect is becoming an increasingly important factor that restricts the development of ADCs. The pursuit of ADCs with optimal therapeutic windows has resulted in remarkable progress in the discovery and development of novel linkers. The present review summarizes the advance of the chemical trigger, linker‒antibody attachment and linker‒payload attachment over the last 5 years, and describes the ADMET properties of ADCs. This work also helps clarify future developmental directions for the linkers. Antibody-drug conjugates (ADCs) are gradually revolutionizing clinical cancer therapy. The antibody-drug conjugate linker molecule determines both the efficacy and the adverse effects, and so has a major influence on the fate of ADCs. An ideal linker should be stable in the circulatory system and release the cytotoxic payload specifically in the tumor. However, existing linkers often release payloads nonspecifically and inevitably lead to off-target toxicity. This defect is becoming an increasingly important factor that restricts the development of ADCs. The pursuit of ADCs with optimal therapeutic windows has resulted in remarkable progress in the discovery and development of novel linkers. The present review summarizes the advance of the chemical trigger, linker‒antibody attachment and linker‒payload attachment over the last 5 years, and describes the ADMET properties of ADCs. This work also helps clarify future developmental directions for the linkers.Antibody-drug conjugates (ADCs) are gradually revolutionizing clinical cancer therapy. The antibody-drug conjugate linker molecule determines both the efficacy and the adverse effects, and so has a major influence on the fate of ADCs. An ideal linker should be stable in the circulatory system and release the cytotoxic payload specifically in the tumor. However, existing linkers often release payloads nonspecifically and inevitably lead to off-target toxicity. This defect is becoming an increasingly important factor that restricts the development of ADCs. The pursuit of ADCs with optimal therapeutic windows has resulted in remarkable progress in the discovery and development of novel linkers. The present review summarizes the advance of the chemical trigger, linker‒antibody attachment and linker‒payload attachment over the last 5 years, and describes the ADMET properties of ADCs. This work also helps clarify future developmental directions for the linkers. Antibody–drug conjugates (ADCs) are gradually revolutionizing clinical cancer therapy. The antibody–drug conjugate linker molecule determines both the efficacy and the adverse effects, and so has a major influence on the fate of ADCs. An ideal linker should be stable in the circulatory system and release the cytotoxic payload specifically in the tumor. However, existing linkers often release payloads nonspecifically and inevitably lead to off-target toxicity. This defect is becoming an increasingly important factor that restricts the development of ADCs. The pursuit of ADCs with optimal therapeutic windows has resulted in remarkable progress in the discovery and development of novel linkers. The present review summarizes the advance of the chemical trigger, linker‒antibody attachment and linker‒payload attachment over the last 5 years, and describes the ADMET properties of ADCs. This work also helps clarify future developmental directions for the linkers. Antibody–drug conjugates (ADCs) are revolutionizing cancer therapy. Linkers, determining both efficacy and off-target toxicity, are the core components of ADCs. The advances of linkers over the past 5 years are reviewed. [Display omitted] Antibody–drug conjugates (ADCs) are gradually revolutionizing clinical cancer therapy. The antibody–drug conjugate linker molecule determines both the efficacy and the adverse effects, and so has a major influence on the fate of ADCs. An ideal linker should be stable in the circulatory system and release the cytotoxic payload specifically in the tumor. However, existing linkers often release payloads nonspecifically and inevitably lead to off-target toxicity. This defect is becoming an increasingly important factor that restricts the development of ADCs. The pursuit of ADCs with optimal therapeutic windows has resulted in remarkable progress in the discovery and development of novel linkers. The present review summarizes the advance of the chemical trigger, linker‒antibody attachment and linker‒payload attachment over the last 5 years, and describes the ADMET properties of ADCs. This work also helps clarify future developmental directions for the linkers. Antibody–drug conjugates (ADCs) are revolutionizing cancer therapy. Linkers, determining both efficacy and off-target toxicity, are the core components of ADCs. The advances of linkers over the past 5 years are reviewed. Image 1 |
| Author | Su, Zheng Li, Song Liu, Lianqi Fan, Shiyong Wang, Yanming Xie, Fei Xiao, Dian Zhou, Xinbo |
| Author_xml | – sequence: 1 givenname: Zheng surname: Su fullname: Su, Zheng organization: School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang 110016, China – sequence: 2 givenname: Dian surname: Xiao fullname: Xiao, Dian organization: National Engineering Research Center for the Emergency Drug, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China – sequence: 3 givenname: Fei surname: Xie fullname: Xie, Fei organization: National Engineering Research Center for the Emergency Drug, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China – sequence: 4 givenname: Lianqi surname: Liu fullname: Liu, Lianqi organization: National Engineering Research Center for the Emergency Drug, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China – sequence: 5 givenname: Yanming surname: Wang fullname: Wang, Yanming organization: National Engineering Research Center for the Emergency Drug, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China – sequence: 6 givenname: Shiyong orcidid: 0000-0003-4216-8226 surname: Fan fullname: Fan, Shiyong email: fsyn1996@163.com organization: National Engineering Research Center for the Emergency Drug, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China – sequence: 7 givenname: Xinbo surname: Zhou fullname: Zhou, Xinbo email: zhouxinbo@bmi.ac.cn organization: National Engineering Research Center for the Emergency Drug, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China – sequence: 8 givenname: Song surname: Li fullname: Li, Song organization: School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang 110016, China |
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| Keywords | Linker‒payload attachment Antibody–drug conjugate Linker‒antibody attachment Linker Chemical trigger |
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| PublicationDate_xml | – month: 12 year: 2021 text: 2021-12-01 day: 01 |
| PublicationDecade | 2020 |
| PublicationPlace | Netherlands |
| PublicationPlace_xml | – name: Netherlands |
| PublicationTitle | Acta pharmaceutica Sinica. B |
| PublicationTitleAlternate | Acta Pharm Sin B |
| PublicationYear | 2021 |
| Publisher | Elsevier B.V Elsevier |
| Publisher_xml | – name: Elsevier B.V – name: Elsevier |
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| Snippet | Antibody–drug conjugates (ADCs) are gradually revolutionizing clinical cancer therapy. The antibody–drug conjugate linker molecule determines both the efficacy... Antibody-drug conjugates (ADCs) are gradually revolutionizing clinical cancer therapy. The antibody-drug conjugate linker molecule determines both the efficacy... |
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| SubjectTerms | Antibody–drug conjugate Chemical trigger Linker Linker‒antibody attachment Linker‒payload attachment Review |
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| Title | Antibody–drug conjugates: Recent advances in linker chemistry |
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