Sockolosky Jonathan T, Szoka Francis C
Pharmaceutical Sciences and Pharmacogenomics Graduate Program, University of California, San Francisco, USA; Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, 513 Parnassus Ave., Box 0912, San Francisco, CA, 94143, USA.
Adv Drug Deliv Rev. 2015 Aug 30;91:109-24. doi: 10.1016/j.addr.2015.02.005. Epub 2015 Feb 19.
Immunoglobulin G (IgG)-based drugs are arguably the most successful class of protein therapeutics due in part to their remarkably long blood circulation. This arises from IgG interaction with the neonatal Fc receptor, FcRn. FcRn is the central regulator of IgG and albumin homeostasis throughout life and is increasingly being recognized as an important player in autoimmune disease, mucosal immunity, and tumor immune surveillance. Various engineering approaches that hijack or disrupt the FcRn-mediated transport pathway have been devised to develop long-lasting and non-invasive protein therapeutics, protein subunit vaccines, and therapeutics for treatment of autoimmune and infectious disease. In this review, we highlight the diverse biological functions of FcRn, emerging therapeutic opportunities, as well as the associated challenges of targeting FcRn for drug delivery and disease therapy.
基于免疫球蛋白G(IgG)的药物可以说是最成功的一类蛋白质疗法,部分原因是它们在血液循环中的时间非常长。这源于IgG与新生儿Fc受体FcRn的相互作用。FcRn是一生中IgG和白蛋白稳态的核心调节因子,并且越来越被认为是自身免疫性疾病、黏膜免疫和肿瘤免疫监视中的重要参与者。已经设计出各种劫持或破坏FcRn介导的运输途径的工程方法,以开发长效和非侵入性的蛋白质疗法、蛋白质亚单位疫苗以及用于治疗自身免疫性疾病和传染病的疗法。在这篇综述中,我们强调了FcRn的多种生物学功能、新出现的治疗机会,以及针对FcRn进行药物递送和疾病治疗所面临的相关挑战。