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引用次数: 0
摘要
审查目的:基于抗人类免疫缺陷病毒(HIV)抗体的疗法为目前的抗逆转录病毒药物提供了另一种治疗选择。本综述旨在概述为优化广谱中和抗体而开发的 Fc 和 Fab 工程策略,并讨论临床前和临床研究的最新发现:多特异性抗体,包括双特异性和三特异性抗体、DART分子和BiTE,以及Fc优化抗体,已成为治疗HIV的有前途的候选疗法。这些工程化抗体可与 HIV 包膜蛋白和人类受体上的多个表位结合,从而提高抗体的效力和活性广度。此外,Fc 增强型抗体还能延长半衰期并改善效应器功能。这些新型疗法有可能克服目前抗逆转录病毒药物疗法的局限性,更有效地抑制病毒载量并针对艾滋病病毒感染者的潜伏库。要充分了解这些疗法的安全性和有效性,还需要进一步的研究,但越来越多的证据表明,它们有可能成为治疗艾滋病的一类新疗法。
Engineering strategies of Anti-HIV antibody therapeutics in clinical development.
Purpose of review: Anti-human immunodeficiency virus (HIV) antibody-based therapeutics offer an alternative treatment option to current antiretroviral drugs. This review aims to provide an overview of the Fc- and Fab-engineering strategies that have been developed to optimize broadly neutralizing antibodies and discuss recent findings from preclinical and clinical studies.
Recent findings: Multispecific antibodies, including bispecific and trispecific antibodies, DART molecules, and BiTEs, as well as Fc-optimized antibodies, have emerged as promising therapeutic candidates for the treatment of HIV. These engineered antibodies engage multiple epitopes on the HIV envelope protein and human receptors, resulting in increased potency and breadth of activity. Additionally, Fc-enhanced antibodies have demonstrated extended half-life and improved effector function.
Summary: The development of Fc and Fab-engineered antibodies for the treatment of HIV continues to show promising progress. These novel therapies have the potential to overcome the limitations of current antiretroviral pharmacologic agents by more effectively suppressing viral load and targeting latent reservoirs in individuals living with HIV. Further studies are needed to fully understand the safety and efficacy of these therapies, but the growing body of evidence supports their potential as a new class of therapeutics for the treatment of HIV.
期刊介绍:
Published bimonthly and offering a unique and wide ranging perspective on the key developments in the field, each issue of Current Opinion in HIV and AIDS features hand-picked review articles from our team of expert editors. With six disciplines published across the year – including HIV and ageing, a HIV vaccine, and epidemiology – every issue also contains annotated reference detailing the merits of the most important papers.