Planet Biotechnology Inc., Hayward, CA, USA.
Tulane National Primate Research Center, Covington, LA, USA.
Plant Biotechnol J. 2015 Oct;13(8):1078-93. doi: 10.1111/pbi.12441. Epub 2015 Aug 4.
Immunoadhesins are recombinant proteins that combine the ligand-binding region of a receptor or adhesion molecule with immunoglobulin constant domains. All FDA-approved immunoadhesins are designed to modulate the interaction of a human receptor with its normal ligand, such as Etanercept (Enbrel(®) ), which interferes with the binding of tumour necrosis factor (TNF) to the TNF-alpha receptor and is used to treat inflammatory diseases such as rheumatoid arthritis. Like antibodies, immunoadhesins have long circulating half-lives, are readily purified by affinity-based methods and have the avidity advantages conferred by bivalency. Immunoadhesins that incorporate normal cellular receptors for viruses or bacterial toxins hold great, but as yet unrealized, potential for treating infectious disease. As decoy receptors, immunoadhesins have potential advantages over pathogen-targeted monoclonal antibodies. Planet Biotechnology has specialized in developing anti-infective immunoadhesins using plant expression systems. An immunoadhesin incorporating the cellular receptor for anthrax toxin, CMG2, potently blocks toxin activity in vitro and protects animals against inhalational anthrax. An immunoadhesin based on the receptor for human rhinovirus, ICAM-1, potently blocks infection of human cells by one of the major causes of the common cold. An immunoadhesin targeting the MERS coronavirus is in an early stage of development. We describe here the unique challenges involved in designing and developing immunoadhesins targeting infectious diseases in the hope of inspiring further research into this promising class of drugs.
免疫黏附素是重组蛋白,它将受体或黏附分子的配体结合区与免疫球蛋白恒定区结合在一起。所有获得 FDA 批准的免疫黏附素都旨在调节人类受体与其正常配体的相互作用,例如依那西普(Enbrel(®)),它干扰肿瘤坏死因子(TNF)与 TNF-α受体的结合,用于治疗类风湿关节炎等炎症性疾病。与抗体一样,免疫黏附素有较长的循环半衰期,可通过基于亲和力的方法轻易地进行纯化,并且具有二价赋予的亲合力优势。将正常的细胞受体与病毒或细菌毒素结合的免疫黏附素具有巨大但尚未实现的治疗传染病的潜力。作为诱饵受体,免疫黏附素比针对病原体的单克隆抗体具有潜在优势。Planet Biotechnology 专门使用植物表达系统开发抗感染免疫黏附素。一种结合炭疽毒素细胞受体的免疫黏附素 CMG2 在体外能有效阻断毒素活性,并能保护动物免受吸入性炭疽的侵害。一种基于人鼻病毒受体 ICAM-1 的免疫黏附素能有效地阻断普通感冒的主要原因之一对人体细胞的感染。一种针对中东呼吸综合征冠状病毒的免疫黏附素处于早期开发阶段。我们在这里描述了针对传染病设计和开发免疫黏附素所涉及的独特挑战,希望能激发对这一有前途的药物类别进行进一步的研究。