Camelid Single-Domain Antibodies: Historical Perspective and Future Outlook.
Camelid Single-Domain Antibodies: Historical Perspective and Future Outlook.
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DOI：
10.3389/fimmu.2017.01589
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发表时间：
2017
影响因子：
7.3
通讯作者：
Arbabi-Ghahroudi M
中科院分区：
文献类型：
--
作者：
Arbabi-Ghahroudi M
在过去的二十五年里，人们付出了巨大的努力来了解骆驼重链抗体的许多方面，从它们的生物学、进化和免疫遗传学到它们在各个研究和医学领域的潜在应用。在本文中，我对骆驼单域抗体（sdAb 或 VHH，也广泛称为纳米抗体）自发现以来的发展进行了历史回顾，并讨论了这些独特分子在研究、工业和医学各个领域的优点和缺点。 2001 年，骆驼科动物 sdAb 的商业化呈爆炸式增长，布鲁塞尔自由大学 (VUB) 获得了一系列专利，后来由弗拉姆斯大学间生物技术研究所 (VIB) 接手，2002 年之后，VIB 成立的衍生公司 Ablynx 接手。虽然企业家精神无疑促进了纳米抗体作为适销产品的探索，但知识产权限制可能是这些生物分子的发现与进入制药市场之间相对较长的时间跨度的部分原因。现在预计，第一个基于 VHH 的抗体药物 Caplacizumab（一种用于治疗罕见凝血疾病的二价抗 vWF 抗体）可能会在 2018 年或此后不久获得批准并商业化。这种难以捉摸的首次批准，以及关键专利的到期，可能会极大地改变骆驼科动物 sdAb 的科学和生物医学格局，并为其成为主流生物治疗药物铺平道路。
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 sdAbs 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 biomolecules 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.
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