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Antibody-Drug Conjugates and Immunotoxins pp 117–135Cite as

Linker Technology and Impact of Linker Design on ADC Properties

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Part of the book series: Cancer Drug Discovery and Development ((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.

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Notes

  1. 1.

    Half-degradation period is defined as the period of the twofold decrease of the average DAR value.

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Authors and Affiliations

  1. ImmunoGen, Inc., 830 Winter Street, Waltham, MA, 02451, USA

    Victor S. Goldmacher, Rajeeva Singh, Thomas Chittenden & Yelena Kovtun

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  1. Victor S. Goldmacher
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  2. Rajeeva Singh
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  4. Yelena Kovtun
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Correspondence to Victor S. Goldmacher .

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  1. DNA Way 1, South San Francisco, 94080, California, USA

    Gail Lewis Phillips

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Goldmacher, V.S., Singh, R., Chittenden, T., Kovtun, Y. (2013). Linker Technology and Impact of Linker Design on ADC Properties. In: Phillips, G. (eds) Antibody-Drug Conjugates and Immunotoxins. Cancer Drug Discovery and Development. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-5456-4_7

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