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组织交叉反应(tissue cross reactivity,TCR)是单克隆抗体药物开发过程中临床前安全评价的重要组成部分。TCR试验的目的是发现单抗药物和靶抗原以外表位结合,为体内试验毒副作用的监控提供参考。按照FDA、EMA和CFDA要求,TCR需在新药临床申请Ⅰ期临床试验前完成。近年随着单克隆抗体研发由鼠源型向全人源化单抗的转变和发展,免疫组织化学在很多技术环节上出现了新的问题和挑战。结合自身实际工作的经验和近年来国内外组织交叉反应研究的进展,探讨并总结单抗药物研发中TCR试验中的相多路径体系技术难点的探索和研究经验,期望能为进一步提高我国TCR试验质量,并增加TCR试验对体内毒理学评价及安全用药的参考价值提供一定的参考。
Tissue cross reactivity (TCR) is an important part of the preclinical safety evaluation of monoclonal antibody drugs. The purpose of the TCR test is to find that the monoclonal antibody binds to the epitope of the target antigen and provides a reference for monitoring the toxic side effects in vivo. According to the requirements of FDA, EMA and CFDA, TCR should be completed before clinical trial of new drug is applied. In recent years, with the development and transformation of murine monoclonal antibodies to fully humanized monoclonal antibodies, immunohistochemistry has emerged new problems and challenges in many technical aspects. Based on the experience of its own work and the progress of cross-reactivity research at home and abroad in recent years, this paper explores and summarizes the technical difficulties of phase-multipath system in the research and development of monoclonal antibody drug discovery and research experience. It is expected that in order to further improve the TCR test Quality, and increase TCR test for toxicology in vivo evaluation and reference value of safe medication to provide some reference.