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Front. Immunol. | doi: 10.3389/fimmu.2017.01589

Camelid Single-Domain Antibodies: Historical Perspective and Future Outlook

  • 1Human Health Therapeutics Portfolio, National Research Council Canada (NRC-CNRC), Canada

Tremendous effort has been expended over the past two and a half decades to understand many aspects of camelid heavy chain antibodies, from their biology, evolution and immunogenetics to their potential applications in various fields of research and medicine. In this article, I present a historical perspective on the development of camelid single-domain antibodies (sdAbs or VHHs, also widely known as nanobodies) since their discovery and discuss the advantages and disadvantages of these unique molecules in various areas of research, industry and medicine. Commercialization of camelid single-domain antibodies exploded in 2001 with a flurry of patents issued to the Vrije Universiteit Brussel (VUB) and later taken on by the Vlaams Interuniversitair Instituut voor Biotechnologie (VIB) and, after 2002, the VIB-founded spin-off company, Ablynx. While entrepreneurial spirit has certainly catalyzed the exploration of nanobodies as marketable products, IP restrictions may be partially responsible for the relatively long time span between the discovery of these bio-molecules and their entry into the pharmaceutical market. It is now anticipated that the first VHH-based antibody drug, Caplacizumab, a bivalent anti-vWF antibody for treating rare blood clotting disorders, may be approved and commercialized in 2018 or shortly thereafter. This elusive first approval, along with the expiry of key patents, may substantially alter the scientific and biomedical landscape surrounding camelid sdAbs and pave the way for their emergence as mainstream biotherapeutics.

Keywords: Camelid single-domain antibody, Heavy-chain antibody, VHH, Nanobody, Antibody engineering, therapeutic antibody

Received: 29 Sep 2017; Accepted: 03 Nov 2017.

Edited by:

Marc H. Van Regenmortel, Centre national de la recherche scientifique (CNRS), France

Reviewed by:

Serge Muyldermans, Vrije Universiteit Brussel, Belgium
Etienne Weiss, Ecole Supérieure de Biotechnologie de Strasbourg, France  

Copyright: © 2017 Arbabi Ghahroudi. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Mehdi Arbabi Ghahroudi, National Research Council Canada (NRC-CNRC), Human Health Therapeutics Portfolio, 100 Sussex Drive, Room 3031, Ottawa, K1A 0R6, Ontario, Canada, mehdi.arbabi@nrc-cnrc.gc.ca