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工程抗体在 HIV-1 治疗和治愈中的潜力。

The potential of engineered antibodies for HIV-1 therapy and cure.

机构信息

Department of Medical Microbiology, Amsterdam University Medical Centers, Location AMC, University of Amsterdam, Amsterdam, 1105 AZ, The Netherlands.

Department of Medical Microbiology, Amsterdam University Medical Centers, Location AMC, University of Amsterdam, Amsterdam, 1105 AZ, The Netherlands.

出版信息

Curr Opin Virol. 2019 Oct;38:70-80. doi: 10.1016/j.coviro.2019.07.007. Epub 2019 Aug 15.

Abstract

Broadly neutralizing antibodies (bnAbs) are currently under investigation as a therapy for HIV-1 infection and recent clinical trials have shown prolonged viral suppression by bnAbs during antiretroviral treatment interruption. Interestingly, these bnAbs also showed the ability to activate the host immune system to clear HIV-1 infected cells. There are many possibilities to further increase the potential efficacy of bnAbs. Most notably, Fc domain engineering to improve half-life and increase engagement of effector cells will augment two advantages of bnAbs. Moreover, antibody engineering can improve affinity and recognition of conserved epitopes and allows the combination of multiple epitope specificities in a single molecule. These increasingly potent and broad antibodies may prove valuable as alternative HIV-1 therapeutic and possibly in curative approaches.

摘要

广谱中和抗体(bnAbs)目前正在作为治疗 HIV-1 感染的一种方法进行研究,最近的临床试验表明,bnAbs 在抗逆转录病毒治疗中断期间可延长病毒抑制。有趣的是,这些 bnAbs 还显示出激活宿主免疫系统清除 HIV-1 感染细胞的能力。有许多方法可以进一步提高 bnAbs 的潜在疗效。最值得注意的是,Fc 结构域工程可以提高半衰期并增加效应细胞的参与,从而增强 bnAbs 的两个优势。此外,抗体工程可以提高对保守表位的亲和力和识别能力,并允许在单个分子中组合多个表位特异性。这些越来越有效和广泛的抗体可能作为替代 HIV-1 治疗方法并可能在治愈方法中具有重要价值。

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