CD20分子模拟表位肽的筛选及其疫苗构建

发布时间：2018-03-09 12:09

本文选题：人淋巴细胞分化抗原CD20　切入点：单克隆抗体Rituximab　出处：《第四军医大学》2006年博士论文　论文类型：学位论文

【摘要】：人淋巴细胞分化抗原CD20仅表达于正常以及95％以上的恶性B细胞表面，是细胞表面非糖基化疏水磷蛋白，分子量为33—37kD，起始表达于pre—B细胞阶段，到B细胞终末分化成浆细胞时消失，，是B细胞的标志性分子。CD20抗原在恶性B细胞表面具有稳定表达、不脱落、不分泌的特性。该分子的第三和第四跨膜区之间，由43个氨基酸残基组成的膜外区，构成了其主要的抗原表位，可以使抗体最大限度地接近细胞膜。因此，CD20分子是恶性B细胞肿瘤治疗最为理想的一个靶抗原。1997年，针对B细胞CD20抗原研制的单克隆抗体Rituximab成为被FDA第一个批准用于B细胞淋巴瘤的治疗，并在临床应用中取得了良好的治疗效果。但单抗治疗的费用高、剂量大、需反复注射以及免疫原性反应极大的限制了单抗的临床应用。因而，构建针对CD20分子的治疗性疫苗，刺激宿主免疫系统产生针对肿瘤的特异性体液免疫反应并对该肿瘤抗原形成长期的免疫记忆，用主动免疫的方式克服单抗应用的不足具有良好的发展前景。模拟表位疫苗是近年来随着噬菌体肽库技术发展起来的一类疫苗，它可以在构象上模拟天然抗原，诱导相应天然表位特异性的体液免疫反应。而且由于模拟表位分子小可以直接以化学合成的方式得到，与传统疫苗以及基因工程产品相比它造价低、工艺简单、质量控制容易，具有工艺稳定、
[Abstract]:Human lymphocytic differentiation antigen (CD20) was expressed only on the surface of normal and malignant B cells above 95%, and was a non-glycosylated hydrophobic phosphorous protein with molecular weight of 33-37 KD, which was expressed at the stage of pre-B cells and disappeared at the end of B cell differentiation into plasma cells. CD20 antigen, the iconic molecule of B cell, has the characteristics of stable expression, no exfoliation and no secretion on the surface of malignant B cell. Between the third and 4th transmembrane regions of the molecule, the extracellular region is composed of 43 amino acid residues. Thus, CD20 molecule is the most ideal target antigen for malignant B cell tumor treatment. In 1997, Rituximab, a monoclonal antibody developed for B cell CD20 antigen, has been the first approved by FDA for the treatment of B cell lymphoma, and has achieved a good therapeutic effect in clinical application. The need for repeated injections and immunogenicity greatly limits the clinical use of McAbs. Therefore, therapeutic vaccines against CD20 molecules are constructed. Stimulating the host immune system to produce a specific humoral immune response to the tumor and to form a long-term immune memory of the tumor antigen, it has a good prospect to overcome the shortcomings of the application of the monoclonal antibody by active immunity. Mimic epitope vaccine is a kind of vaccine developed in recent years with phage peptide library technology. It can mimic natural antigen in conformation. Moreover, the mimic epitope molecules can be obtained directly by chemical synthesis. Compared with traditional vaccines and genetic engineering products, the mimic epitopes are of low cost, simple process and easy quality control. With stable process,
【学位授予单位】：第四军医大学
【学位级别】：博士
【学位授予年份】：2006
【分类号】：R392

【共引文献】