Linker Technology and Impact of Linker Design on ADC Properties

  • Victor S. Goldmacher
  • Rajeeva Singh
  • Thomas Chittenden
  • Yelena Kovtun
Chapter
Part of the Cancer Drug Discovery and Development book series (CDD&D)

Abstract

The function of a linker in an antibody–drug conjugate is to covalently connect its effector moiety, the cytotoxic drug, with its targeting moiety, the antibody. In this chapter, we review various linkers, cleavable and non-cleavable, that have been reported, main approaches that have been used to attach the linkers to the antibodies, and the impact of various linkers on the properties of the resulting ADCs, such as their cytotoxic and antitumor activities, stabilities in circulation and tissues, and the extent of killing of bystander cells and of multidrug-resistant cells. Finally, we review clinical experience with ADCs made with different linkers.

Keywords

Cysteine Lysine Doxorubicin Thiol Cyclohexane 

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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Victor S. Goldmacher
    • 1
  • Rajeeva Singh
    • 1
  • Thomas Chittenden
    • 1
  • Yelena Kovtun
    • 1
  1. 1.ImmunoGen, Inc.WalthamUSA

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