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首页> 外文期刊>Current opinion in HIV and AIDS >CCR5 monoclonal antibodies for HIV-1 therapy.
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CCR5 monoclonal antibodies for HIV-1 therapy.

机译：用于HIV-1治疗的CCR5单克隆抗体。

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PURPOSE OF REVIEW: To summarize emerging clinical and preclinical data pertaining to the use of CCR5 monoclonal antibodies (mAbs) as therapies for HIV-1 infection. The epitope specificity of CCR5 mAbs is discussed in relation to its critical impact on antiviral activity and CCR5 antagonism. We compare and contrast mAbs and small-molecule CCR5 antagonists in terms of their binding and antiviral properties. Two CCR5 mAbs have entered clinical testing and have successfully completed proof-of-concept studies in HIV-infected individuals, providing initial information on the potential therapeutic utility of these agents. RECENT FINDINGS: New studies support the view that the most potent antiviral CCR5 mAbs recognize the second extracellular loop of CCR5 either exclusively or in combination with the amino terminus. Studies have revealed fundamental differences in how mAbs and small molecules bind CCR5 and inhibit HIV-1. CCR5 mAbs and small-molecule CCR5 antagonists have demonstrated consistent antiviral synergy and limited or no viral cross-resistance in independent studies. Single intravenous infusions of CCR5 mAbs significantly reduced HIV-1 RNA levels in infected individuals for 2-3 weeks without appreciable toxicity. SUMMARY: CCR5 mAbs have demonstrated broad and potent antiviral activity in vitro. Clinical studies have established CCR5 mAbs as potent antiretroviral agents with prolonged activity following a single dose. CCR5 mAbs represent both a distinct class of CCR5 inhibitor and a novel approach to HIV-1 therapy.
机译：审查目的：总结与使用CCR5单克隆抗体（mAb）作为HIV-1感染疗法有关的新兴临床和临床前数据。讨论了CCR5 mAb的表位特异性及其对抗病毒活性和CCR5拮抗作用的关键影响。我们比较和对比单克隆抗体和小分子CCR5拮抗剂的结合和抗病毒特性。两种CCR5 mAb已进入临床测试，并已成功完成了对HIV感染者的概念验证研究，从而提供了有关这些药物潜在治疗用途的初步信息。最近的发现：最新研究支持以下观点：最有效的抗病毒CCR5 mAb可以单独或与氨基末端结合识别CCR5的第二个细胞外环。研究表明，mAb和小分子结合CCR5和抑制HIV-1的方式存在根本差异。在独立的研究中，CCR5 mAb和小分子CCR5拮抗剂表现出一致的抗病毒协同作用，并且病毒交叉耐药性有限或没有。 CCR5 mAb的单次静脉输注可在2-3周内显着降低感染个体的HIV-1 RNA水平，而无明显毒性。摘要：CCR5单克隆抗体在体外已显示出广泛而有效的抗病毒活性。临床研究已确定CCR5 mAbs为有效的抗逆转录病毒药物，单剂给药后具有延长的活性。 CCR5 mAb既代表一类独特的CCR5抑制剂，又代表一种新的HIV-1治疗方法。

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