Nanobodies®† as inhaled biotherapeutics for lung diseases
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- 作者：Gino Van Heeke ; gino.vanheeke@ablynx.com ; Koen Allosery ; Veronique De Brabandere ; Tim De Smedt ; Laurent Detalle ; Antonin de Fougerolles
- 关键词：GSD ; Geometric standard deviation ; HCAb ; Heavy chain-only antibody ; HMWs ; Higher molecular weight variants ; mAb ; Monoclonal antibody ; NGI ; Next-generation impactor ; RP-HPLC ; Reverse-phase high-performance liquid chromatography ; RSV ; Respiratory syncytial virus ; SE-HPLC ; Size exclusion high-performance liquid chromatography ; VMD ; Volume median diameter
- 刊名：Pharmacology & Therapeutics
- 出版年：2017
- 出版时间：January 2017
- 年：2017
- 卷：169
- 期：Complete
- 页码：47-56
- 全文大小：975 K
- 卷排序：169
文摘
Local pulmonary delivery of biotherapeutics may offer advantages for the treatment of lung diseases. Delivery of the therapeutic entity directly to the lung has the potential for a rapid onset of action, reduced systemic exposure and the need for a lower dose, as well as needleless administration. However, formulation of a protein for inhaled delivery is challenging and requires proteins with favorable biophysical properties suitable to withstand the forces associated with formulation, delivery, and inhalation devices. Nanobodies are the smallest functional fragments derived from a naturally occurring heavy chain-only immunoglobulin. They are highly soluble, stable, and show biophysical characteristics that are particularly well suited for pulmonary delivery. This paper highlights a number of clinical and preclinical studies on antibodies delivered via the pulmonary route and describes the advantages of using Nanobodies for inhaled delivery to the lung. The latter is illustrated by the specific example of ALX-0171, a Nanobody in clinical development for the treatment of respiratory syncytial virus (RSV) infections.