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16 - Single-Domain Antibodies

from PART VI - NOVEL ANTIBODY FORMATS

Published online by Cambridge University Press:  15 December 2009

By
Serge Muyldermans ,
Gholamreza Hassanzadeh Ghassabeh  and
Dirk Saerens
Edited by
Melvyn Little
Melvyn Little
Affiliation:
Affimed Therapeutics AG
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Summary

The antigen-binding entity of an antibody, reduced in size to one single domain, is referred to as a “single-domain antibody.” Various strategies have been explored with variable success to arrive at functional single-domain antibodies. The potential of single-domain antibodies, as research tools or in medicine, is reflected by the three companies – founded in Europe – with a mission to bring these molecules to the market. Domantis using human VH-derived single-domain antibodies started in 2000 and was bought by GSK for £300M in December 2007. Haptogen employing shark single-domain antibodies was acquired by Wyeth, and Ablynx focusing on llama-derived single-domain antibodies received over €70M in three rounds of venture capitalist investments and another €80M on the Euronext stock market in November 2007. Regarding therapeutic applications, Arana Therapeutics in Australia entered a Phase 2 clinical trial with its single-domain antibody derivative. In this chapter, we will review (1) the various antibodies used for generating single-domain antibodies, (2) the properties of single-domain antibodies that create an added value for use in immunotherapy, and (3) a number of therapeutic applications.

THE DEVELOPMENT OF SINGLE-DOMAIN ANTIBODIES

Antibodies comprise two identical heavy chain polypeptides (H) carrying chains of carbohydrates and two identical light chain proteins (L). Their ability to bind specifically to an antigen is dictated by the paired variable regions of the heavy (VH) and the light (VL) chain (Figure 16.1).

Type
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Recombinant Antibodies for Immunotherapy , pp. 216 - 230
Publisher: Cambridge University Press
Print publication year: 2009

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