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基于新型蛋白质支架的治疗药物开发的最新进展。

Recent advances in the development of novel protein scaffolds based therapeutics.

作者信息

Azhar Asim, Ahmad Ejaj, Zia Qamar, Rauf Mohd Ahmar, Owais Mohammad, Ashraf Ghulam Md

机构信息

Interdisciplinary Biotechnology Unit, Aligarh Muslim University, Aligarh, UP, India.

Interdisciplinary Biotechnology Unit, Aligarh Muslim University, Aligarh, UP, India.

出版信息

Int J Biol Macromol. 2017 Sep;102:630-641. doi: 10.1016/j.ijbiomac.2017.04.045. Epub 2017 Apr 13.

Abstract

Antibodies occupy a central position when it comes to binding proteins with desired antigenic specificities. During the past decade, a plethora of recombinant or humanized versions of antibodies have entered clinical settings with outstanding accomplishments. Yet, they suffer from several drawbacks such as high molecular weight, limited tissue penetration, instability, high production cost, requirement for large doses and potential cytotoxicity. As a result, new generation of receptor proteins has been developed, that are derived from small and robust immunoglobulin (Ig) or non-immunoglobulin based "scaffolds". Combinatorial protein engineering has tremendous scope in the development of these protein scaffolds with immunoglobulin like specificity and/or prescribed binding functions. The advancement made in this regard can boast of developing various validated Ig based and non-Ig protein scaffolds with desirable therapeutic potential. The newly emerging technology has profound scope in translational biology and offer matching replacement for existing immunotherapeutic agents. Only few data from early clinical studies are available yet, but many more are likely to come in the near future. Here, we provide a glimpse of recent clinical advances in the field of existing protein scaffolds.

摘要

在结合具有所需抗原特异性的蛋白质方面,抗体占据着核心地位。在过去十年中,大量重组或人源化抗体已进入临床应用,并取得了显著成就。然而,它们存在一些缺点,如分子量高、组织穿透力有限、稳定性差、生产成本高、需要大剂量使用以及潜在的细胞毒性。因此,新一代受体蛋白已被开发出来,这些受体蛋白源自小型且稳定的免疫球蛋白(Ig)或基于非免疫球蛋白的“支架”。组合蛋白工程在开发具有免疫球蛋白样特异性和/或特定结合功能的这些蛋白支架方面具有巨大潜力。在这方面取得的进展包括开发了各种经过验证的基于Ig和非Ig的蛋白支架,具有理想的治疗潜力。这项新兴技术在转化生物学中具有深远的应用前景,可为现有免疫治疗药物提供合适的替代品。目前仅有少数早期临床研究的数据,但在不久的将来可能会有更多数据出现。在此,我们简要介绍一下现有蛋白支架领域最近的临床进展。

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