单克隆抗体的研究进展及上市药物分析

Advances of monoclonal antibodies and analysis of marketed antibody drugs

摘要:

近年来全球各地新冠、猴痘、流感等疫情频发，新增各类肿瘤患者数量呈不断上升趋势，传统药物对新发突发传染病、肿瘤、自身免疫病等的作用有限。随着杂交瘤技术的出现，单克隆抗体的应用日趋广泛，抗体药物在现代医学中发挥着越来越重要的作用。单克隆抗体经历了鼠源抗体、人鼠嵌合抗体、人源化抗体、全人源抗体的发展阶段，其免疫原性逐渐下降，用于人体的安全性逐渐上升。全人源抗体由于其序列均来自于人，不会产生人抗鼠抗体反应，成为了目前最安全的抗体形式。随着基因工程技术的发展，流式细胞术结合单个B细胞基因扩增技术使全人源单克隆抗体的构建和筛选更为容易，抗体药物的发展迎来新一波高潮，单克隆抗体药物的市场将会进一步扩展。本文综述了单克隆抗体的研究进展以及截至2023年10月1日美国食品药品监督管理局(Food and Drug Administration, FDA)批准的163种单抗药物，为国内单克隆抗体的研发及生产提供新的思路。

Abstract:

In recent years, there has been a frequent occurrence of various epidemics worldwide such as COVID-19, monkeypox, influenza, and others additionally, there has been an increase in the number of new patients diagnosed with various types of tumors. Traditional drugs have limited effectiveness against emerging infectious diseases, tumors, and autoimmune diseases. However, with the emergence of hybridoma technology, monoclonal antibodies have achieved extensive applications and antibody drugs are playing an important role in modern medicine. Monoclonal antibodies have undergone various development stages, starting from mouse-derived antibodies to human-mouse chimeric antibodies, humanized antibodies, and ultimately human antibodies. Throughout this process, their immunogenicity has gradually decreased, while their safety for human use steadily increased. Fully human antibodies are currently the safest form of antibody, because their sequences all come from human sources and they do not induce human anti-murine antibody reactions. With the advance of genetic engineering technology, flow cytometry coupled to single B cell gene amplification technology has made it easier to construct and screen for fully human monoclonal antibodies. The development of antibody drugs has provided new opportunities, and the market for monoclonal antibody drugs will further expand. This article reviews the research progress of monoclonal antibodies and presents information on the 163 monoclonal antibody drugs approved by the United States Food and Drug Administration (FDA) as of Oct 1^st, 2023. The aim is to offer new insights for the development and production of monoclonal antibodies in China.