Journal of Radiopharmaceuticals and Molecular Probes (대한방사성의약품학회지)

Korean Society of Radiopharmaceuticals and Molecular Probes (대한방사성의약품학회)
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Recent progress of enzyme cleavable linker in antibody-drug conjugates: sulfatase and phosphatase

  • Sushil K. Dwivedi (Department of Molecular Medicine, Brain Korea 21 four KNU Convergence Educational Program of Biomedical Sciences for Creative Future Talents, School of Medicine, Kyungpook National University) ;
  • Abhinav Bhise (Department of Molecular Medicine, Brain Korea 21 four KNU Convergence Educational Program of Biomedical Sciences for Creative Future Talents, School of Medicine, Kyungpook National University) ;
  • Rajkumar Subramani (Department of Molecular Medicine, Brain Korea 21 four KNU Convergence Educational Program of Biomedical Sciences for Creative Future Talents, School of Medicine, Kyungpook National University) ;
  • Jeongsoo Yoo (Department of Molecular Medicine, Brain Korea 21 four KNU Convergence Educational Program of Biomedical Sciences for Creative Future Talents, School of Medicine, Kyungpook National University)
  • Received : 2021.05.31
  • Accepted : 2021.06.28
  • Published : 2021.06.30
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Abstract

Recently, antibody-drug conjugates (ADCs) are used to deliver efficient cytotoxic payloads selectively in cancer cells. In the designing of an ADC, the antibody is connected to a toxic payload via a covalent linker, which helps to solubilizes the typical hydrophobic payload as well as stabilizes the linkage over circulation. The development of the linkers for the antibody drug conjugate is still in demand. Initially, the acid, disulfide, and cathepsin-sensitive ADCs attracted considerable attention for the delivery of a potent cytotoxic payload but suffer from instability in human and mouse plasma with a short half-life. In addition, It also suffer from a solubility issue that induces aggregation, which is the major problem in their development. ADCs associated with sulfatase and phosphatase cleavable linker are highly soluble due to the anionic nature of sulfate and phosphate groups. The ADCs also showed high stability in human and mouse plasma. Therefore, to overcome these limitations, sulfatase and phosphatase cleavable linkers were developed. This review focuses on the recently reported advantages of sulfatase and phosphatase cleavable linkers for ADCs.

Keywords

Acknowledgement

This work was supported by an R&D program through the National Research Foundation of Korea funded by the Ministry of Science, ICT & Future Planning (No. 2019R1A2C2084313, 2020M2D8A3094031 and 2020R1C1C1008442).

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