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单克隆抗体治疗慢性阻塞性肺疾病的安全性与有效性概述

An Overview of the Safety and Efficacy of Monoclonal Antibodies for the Chronic Obstructive Pulmonary Disease.

作者信息

Cazzola Mario, Ora Josuel, Cavalli Francesco, Rogliani Paola, Matera Maria Gabriella

机构信息

Chair of Respiratory Medicine, Department of Experimental Medicine, University of Rome Tor Vergata, Rome, Italy.

Division of Respiratory Medicine, University Hospital Tor Vergata, Rome, Italy.

出版信息

Biologics. 2021 Aug 27;15:363-374. doi: 10.2147/BTT.S295409. eCollection 2021.

Abstract

Several mAbs have been tested or are currently under clinical evaluation for the treatment of COPD. They can be subdivided into those that aim to block specific pro-inflammatory and pro-neutrophilic cytokines and chemokines, such as TNF-α, IL-1β, CXCL8 and IL-1β, and those that act on T2-mediated inflammation, respectively, by blocking IL-5 and/or its receptor, preventing IL-4 and IL-13 signaling, affecting IL-33 pathway and blocking TSLP. None of these approaches has proved to be effective, probably because in COPD there is no dominant cytokine or chemokine and, therefore, a single mAb cannot be effective on all pathways. With a more in-depth understanding of the numerous pheno/endotypic pathways that play a role in COPD, it may eventually be possible to identify those specific patients in whom some of these cytokines or chemokines might predominate. In this case, it will be possible to implement a personalized treatment, but the use of each mAb will only be reserved for a very limited number of subjects.

摘要

几种单克隆抗体已被测试或目前正在进行治疗慢性阻塞性肺疾病(COPD)的临床评估。它们可分为旨在阻断特定促炎和促中性粒细胞细胞因子及趋化因子的抗体,如肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)、CXC趋化因子配体8(CXCL8)和IL-1β,以及分别通过阻断IL-5和/或其受体、阻止IL-4和IL-13信号传导、影响IL-33途径和阻断胸腺基质淋巴细胞生成素(TSLP)来作用于2型介导炎症的抗体。这些方法均未被证明有效,可能是因为在COPD中不存在占主导地位的细胞因子或趋化因子,因此,单一的单克隆抗体不可能对所有途径都有效。随着对在COPD中起作用的众多表型/内型途径有更深入的了解,最终有可能确定其中某些细胞因子或趋化因子可能占主导地位的特定患者。在这种情况下,将有可能实施个性化治疗,但每种单克隆抗体的使用将仅保留给极少数患者。

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