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细胞因子风暴靶向抗体的使用和风险相关问题的观点,以及针对 COVID-19 临床病例治疗开发新型单克隆抗体所面临的挑战。

Perspectives on the use and risk of adverse events associated with cytokine-storm targeting antibodies and challenges associated with development of novel monoclonal antibodies for the treatment of COVID-19 clinical cases.

机构信息

Department of Veterinary Medicine, College of Food and Agriculture, United Arab Emirates University, Abu Dhabi, United Arab Emirates.

出版信息

Hum Vaccin Immunother. 2021 Sep 2;17(9):2824-2840. doi: 10.1080/21645515.2021.1908060. Epub 2021 May 11.

Abstract

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the novel coronavirus disease 2019 (COVID-19) pandemic that lacks globally accessible effective antivirals or extensively available vaccines. Numerous clinical trials are exploring the applicability of repurposed monoclonal antibodies (mAbs) targeting cytokines that cause adverse COVID-19-related pathologies, and novel mAbs directly targeting SARS-CoV-2. However, comorbidities and the incidence of cytokine storm (CS)-associated pathological complexities in some COVID-19 patients may limit the clinical use of these drugs. Additionally, CS-targeting mAbs have the potential to cause adverse events that restrict their applicability in patients with comorbidities. Novel mAbs targeting SARS-CoV-2 require pharmacological and toxicological characterization before a marketable product becomes available. The affordability of novel mAbs across the global economic spectrum may seriously limit their accessibility. This review presents a perspective on antibody-based research efforts and their limitations for COVID-19.

摘要

严重急性呼吸综合征冠状病毒 2(SARS-CoV-2)是导致 2019 年新型冠状病毒病(COVID-19)大流行的病原体,目前缺乏全球可获得的有效抗病毒药物或广泛可用的疫苗。许多临床试验正在探索针对细胞因子的重新利用单克隆抗体(mAbs)的适用性,这些细胞因子会导致 COVID-19 相关的病理变化,以及直接针对 SARS-CoV-2 的新型 mAbs。然而,一些 COVID-19 患者的合并症和细胞因子风暴(CS)相关病理复杂性的发生率可能会限制这些药物的临床应用。此外,靶向 CS 的 mAbs 有可能引起不良反应,从而限制了它们在合并症患者中的适用性。针对 SARS-CoV-2 的新型 mAbs 在可销售产品上市之前需要进行药理学和毒理学特征分析。新型 mAbs 在全球经济范围内的可负担性可能会严重限制其可及性。本文就抗体为基础的研究工作及其在 COVID-19 方面的局限性提出了观点。

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