全人源抗MAGE-A1单链抗体的筛选及免疫活性鉴定

发布时间：2018-02-14 12:49

本文关键词： MAGE-A1 肿瘤噬菌体抗体库单链抗体全人抗体亲和常数　出处：《南京医科大学》2005年硕士论文　论文类型：学位论文

【摘要】：MAGE-Al为MAGE(melanoma associated antigen)家族中的一员,在多种肿瘤组织均有不同程度表达,但在正常组织中除睾丸和胎盘外均不表达。因此,MAGE-Al抗原有可能作为肿瘤免疫治疗的靶点。免疫治疗是继手术、化疗、放疗之后的第四种肿瘤治疗模式,但是鼠源性单克隆抗体对人体有免疫原性,既会产生人抗鼠抗体诱发过敏反应,又不能有效激活人体的生物效应功能,在人体内的半衰期也较短。鼠源性抗体的这些自身局限性极大地限制了其作为治疗制剂在人体内的应用。1991年Winter等创立的噬菌体抗体库技术,以大肠杆菌作为宿主,丝状噬菌体作为表达和展示的载体,使得抗体以及编码抗体的DNA,共同存在于宿主菌中。噬菌体抗体库技术使得产生全人源抗体成为可能。全人源噬菌体抗体库用细菌克隆取代B细胞克隆表达抗体,不经细胞融合,甚至不经免疫,可以制备针对任何抗原的全人源抗体,对人体没有免疫原性,不会引起过敏反应,可直接用于人体内。本课题在参照国内外相关研究的基础上,以期从全人源单链噬菌体抗体库中筛选出特异性抗MAGE-Al单链抗体,为肿瘤的免疫治疗提供技术储备。研究目的 1.应用噬菌体抗体库技术,筛选出全人源抗MAGE-Al噬菌体抗体,鉴定其免疫活性。
[Abstract]:MAGE-Al is a member of MAGE(melanoma associated antigen. it is expressed in various tumor tissues, but not in normal tissues except testis and placenta. Therefore, MAGE-Al antigen may be used as a target of tumor immunotherapy. There are 4th kinds of tumor treatment modes after chemotherapy and radiotherapy, but mouse monoclonal antibody has immunogenicity to human body, it can not only produce human anti-mouse antibody to induce allergic reaction, but also can not effectively activate the biological effect function of human body. In 1991, Winter and other phage antibody library techniques were created to use Escherichia coli as host. Filamentous phage as expression and display vector, The technique of phage antibody library makes it possible to produce whole human antibody. The whole human phage antibody library uses bacterial clone instead of B cell clone to express antibody without cell fusion. Even without immunity, the whole human antibody against any antigen can be prepared, and it has no immunogenicity to the human body and will not cause allergic reaction, so it can be directly used in human body. The aim of this study was to screen the specific anti MAGE-Al single chain antibody from the whole human single chain phage antibody library and to provide a technical reserve for tumor immunotherapy. Research purpose. 1. The whole human anti MAGE-Al phage antibody was screened by phage antibody library technique and its immunological activity was identified.
【学位授予单位】：南京医科大学
【学位级别】：硕士
【学位授予年份】：2005
【分类号】：R392

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