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基于单克隆抗体的细菌脓毒症治疗方法的最新进展

Recent Advances in Monoclonal Antibody-Based Approaches in the Management of Bacterial Sepsis.

作者信息

Kharga Kusum, Kumar Lokender, Patel Sanjay Kumar Singh

机构信息

School of Biotechnology, Faculty of Applied Sciences and Biotechnology, Shoolini University, Solan 173229, Himachal Pradesh, India.

Cancer Biology Laboratory, Raj Khosla Centre for Cancer Research, Shoolini University, Solan 173229, Himachal Pradesh, India.

出版信息

Biomedicines. 2023 Mar 2;11(3):765. doi: 10.3390/biomedicines11030765.

Abstract

Sepsis is a life-threatening condition characterized by an uncontrolled inflammatory response to an infectious agent and its antigens. Immune cell activation against the antigens causes severe distress that mediates a strong inflammatory response in vital organs. Sepsis is responsible for a high rate of morbidity and mortality in immunosuppressed patients. Monoclonal antibody (mAb)-based therapeutic strategies are now being explored as a viable therapy option for severe sepsis and septic shock. Monoclonal antibodies may provide benefits through two major strategies: (a) monoclonal antibodies targeting the pathogen and its components, and (b) mAbs targeting inflammatory signaling may directly suppress the production of inflammatory mediators. The major focus of mAb therapies has been bacterial endotoxin (lipopolysaccharide), although other surface antigens are also being investigated for mAb therapy. Several promising candidates for mAbs are undergoing clinical trials at present. Despite several failures and the investigation of novel targets, mAb therapy provides a glimmer of hope for the treatment of severe bacterial sepsis and septic shock. In this review, mAb candidates, their efficacy against controlling infection, with special emphasis on potential roadblocks, and prospects are discussed.

摘要

脓毒症是一种危及生命的病症,其特征为对感染因子及其抗原产生不受控制的炎症反应。针对抗原的免疫细胞激活会引发严重不适,进而在重要器官介导强烈的炎症反应。脓毒症是免疫抑制患者发病和死亡的主要原因。基于单克隆抗体(mAb)的治疗策略目前正在作为重症脓毒症和脓毒性休克的一种可行治疗选择进行探索。单克隆抗体可通过两种主要策略发挥作用:(a)靶向病原体及其成分的单克隆抗体,以及(b)靶向炎症信号传导的单克隆抗体可直接抑制炎症介质的产生。单克隆抗体治疗的主要重点一直是细菌内毒素(脂多糖),不过其他表面抗原也在进行单克隆抗体治疗研究。目前有几种有前景的单克隆抗体候选药物正在进行临床试验。尽管经历了几次失败以及对新靶点的研究,但单克隆抗体治疗为重症细菌性脓毒症和脓毒性休克的治疗带来了一线希望。在本综述中,将讨论单克隆抗体候选药物、它们在控制感染方面的疗效,特别强调潜在障碍以及前景。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dcc7/10045367/4e54e5c7b313/biomedicines-11-00765-g001.jpg

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