单克隆抗体技术的诞生、现状和展望  

Monoclonal antibodies:Emergence present and outlook

作　　者：高吉 何娟 王庆文[2] 刘万里[1] Ji Gao;Juan He;Qingwen Wang;Wanli Liu(Institute for Immunology,School of Life Sciences,Tsinghua-Peking Center for Life Sciences,Tsinghua University,Beijing 100084,China;Department of Rheumatism and Immunology,Peking University Shenzhen Hospital,Shenzhen 518036,China)

机构地区：[1]清华大学生命科学学院,免疫学研究所,清华-北大生命科学联合中心,北京100084 [2]北京大学深圳医院风湿免疫科,深圳518036

出　　处：《科学通报》2020年第28期3085-3090,共7页Chinese Science Bulletin

基　　金：深圳市医疗卫生“三名工程”(SZSM201612009);国家自然科学基金(81621002,31811540397,81974253,81901641)资助

摘　　要：Nature于2019年末选出了其创刊150年历史上出版.过的最具有历史影响力的10篇论文,其中包括剑桥大学的阿根廷生物学家CesarMilstein(色萨·米尔斯坦)和德国生物学家Georges J.F.Kohler(乔治斯·科勒)在1975年发表的文章,他们提出的利用杂交瘤细胞生产单克隆抗体(monoclonal antibody)的方法,为此后半个世纪的免疫学以及癌症和自身免疫性疾病治疗的医学研究提供了重要的工具和思路.此文一经发表,就引发了领域内研究者们的热切关注.当时德国科隆大学(Universitat zu KoIn)的免疫学家Rajewsky在为Nature撰写的新闻稿中这么评论道:“我当时立刻意识到我们的研究领域迎来了一个转折点.”Monoclonal antibodies are of great use in research and clinic.The first monoclonal antibody production method,hy-bridoma technology,was marked in the paper"Continuous cultures of fused cells secreting antibody of predefined speci-ficity"by Milstein and Kohler in 1975 in Nature.Based on that paper,we took a retrospective and forward look of this technique.In the early research of antibodies and B cells,the low specificity and bad reproductivity of polyclonal anti-bodies called for new methods to produce highly specific antibodies.Fortunately,the scientists encountered the key pre-requisites of the hybridoma method:(1)Mouse multiple myeloma cell lines,which can secrete antibodies and infinitely reproduce in vitro;(2)SRBC(sheep red blood cell)plates that can screen the cells secreteing anti-SRBC antibodies;(3)proper cell fusion methods like Sendai virus and PEG.Based on all these materials and methods,Milstein and Kohler fused spleen cells of immunized mice with mouse myeloma cell line P3-X67Ag8 by inactivated Sendai virus and screened to clone the fused cells that can secrete anti-SRBC antibodies.They also used HAT medium to ensure that only fused cells from spleen ells and myeloma cells can survive.In this way,they obtained the immortal cells that can pro-duce a single type of antibody with a predefined antigen-specificity,or say,hybridoma cells that can produce monoclonal antibodies.This powerful tool of hybridoma was quickly applied and improved.Milstein and Kohler were awarded the Nobel prize and Lasker award in 1984.Despite the great commercial potential of hybridoma in medication and science research,Milstein and Kohler did not patent the method,making it free to use by anyone in the world.The monoclonal antibodies produced by hybridoma were proved highly versatile in the laboratory.Besides great insights provided to us in basic immunology research,they become the indispensable tool to precisely qualify,quantify,and localize macromole-cule in all fields of research.Fluorescence imaging,Western blotting,flow c

关 键 词：免疫学家 自身免疫性疾病 单克隆抗体技术 杂交瘤细胞 米尔斯坦 德国生物学家 德国科隆大学 

分 类 号：R392[医药卫生—免疫学]