Suppr超能文献

将治疗性抗体重新设计为可穿透血脑屏障的双特异性抗体用于治疗阿尔茨海默病。

Re-engineering therapeutic antibodies for Alzheimer's disease as blood-brain barrier penetrating bi-specific antibodies.

作者信息

Pardridge William M

机构信息

a Brain Research Institute , University of California , Los Angeles , CA , USA.

出版信息

Expert Opin Biol Ther. 2016 Dec;16(12):1455-1468. doi: 10.1080/14712598.2016.1230195. Epub 2016 Sep 7.

Abstract

Therapeutic antibodies are large molecule drugs that do not cross the blood-brain barrier (BBB). Therefore, drug development of therapeutic antibodies for Alzheimer's disease (AD) requires that these molecules be re-engineered to enable BBB delivery. This is possible by joining the therapeutic antibody with a transporter antibody, resulting in the engineering of a BBB-penetrating bispecific antibody (BSA). Areas covered: The manuscript covers transporter antibodies that cross the BBB via receptor-mediated transport systems on the BBB, such as the insulin receptor or transferrin receptor. Furthermore, it highlights therapeutic antibodies for AD that target the Abeta amyloid peptide, beta secretase-1, or the metabotropic glutamate receptor-1. BSAs are comprised of both the transporter antibody and the therapeutic antibody, as well as IgG constant region, which can induce immune tolerance or trigger transport via Fc receptors. Expert opinion: Multiple types of BSA molecular designs have been used to engineer BBB-penetrating BSAs, which differ in valency and spatial orientation of the transporter and therapeutic domains of the BSA. The plasma pharmacokinetics and dosing regimens of BSAs differ from that of conventional therapeutic antibodies. BBB-penetrating BSAs may be engineered in the future as new treatments of AD, as well as other neural disorders.

摘要

治疗性抗体是无法穿过血脑屏障(BBB)的大分子药物。因此,开发用于治疗阿尔茨海默病(AD)的治疗性抗体需要对这些分子进行重新设计,以实现血脑屏障递送。通过将治疗性抗体与转运抗体连接,从而构建能够穿透血脑屏障的双特异性抗体(BSA),这是可行的。涵盖领域:本文涵盖了通过血脑屏障上的受体介导转运系统(如胰岛素受体或转铁蛋白受体)穿过血脑屏障的转运抗体。此外,还重点介绍了针对淀粉样β肽、β分泌酶-1或代谢型谷氨酸受体-1的AD治疗性抗体。双特异性抗体由转运抗体、治疗性抗体以及IgG恒定区组成,后者可诱导免疫耐受或通过Fc受体触发转运。专家观点:已采用多种类型的双特异性抗体分子设计来构建能够穿透血脑屏障的双特异性抗体,这些双特异性抗体在其转运结构域和治疗结构域的价态和空间取向上存在差异。双特异性抗体的血浆药代动力学和给药方案与传统治疗性抗体不同。未来,能够穿透血脑屏障的双特异性抗体可能被开发用于治疗AD以及其他神经疾病。

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍。

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

文档翻译

学术文献翻译模型,支持多种主流文档格式。

立即体验