活化T细胞选择性清除分子hS83-P34的构建、制备及功能研究

发布时间：2018-06-07 00:26

本文选题：重组免疫毒素 + CTLA-4　；参考：《四川大学》2005年博士论文

【摘要】：免疫抑制剂广泛应用于临床,降低了急性排斥反应的发生率,使移植受者的长期与近期存活率都有所提高,然而免疫抑制剂长期蓄积的毒副作用导致慢性药物性损伤,制约了长期存活率的进一步提高。在供器官严重短缺的情况下,如何有效抑制排斥反应,保证移植物长期有功能存活、改善受者生活质量是器官移植领域亟待解决的问题。寻求更加高效、低毒、低感染、低致瘤危险性的特异性免疫抑制剂已成为当前研究的重点。活化T细胞是介导移植排斥的重要细胞,选择性清除活化T细胞而保留静息细胞,能控制移植排斥反应发生,减少药物的毒副作用。活化T细胞表面诱导性表达CTLA-4分子,基于此,我们设计以anti-CTLA-4单链抗体(scFv)为导向片段、膜孔道形成分子一穿孔素(perforin,pore-forming protein, PFP)孔道形成功能域为杀伤片段的免疫毒素,以选择性清除活化的T细胞。抗CTLA-4抗体能选择性地与活化T细胞结合,膜孔道形成蛋白作为免疫毒素杀伤片段,克服了现有胞内作用杀伤片段毒副作用大、免疫原性强、分子内化效率低的缺点,成为更具优势的杀伤片段。本研究以anti-CTLA-4单链抗体(scFv)为导向片段、穿孔素孔道形
[Abstract]:Immunosuppressants are widely used in clinical practice, reducing the incidence of acute rejection and increasing the long-term and short-term survival rates of transplant recipients. However, the long-term accumulation of immunosuppressive agents leads to chronic drug-induced injury. It restricts the further improvement of long-term survival rate. In the case of serious shortage of donor organs, how to effectively suppress rejection, ensure the long-term functional survival of the graft, and improve the quality of life of the recipient is an urgent problem to be solved in the field of organ transplantation. To seek more efficient, low toxic, low infection, low tumor risk specific immunosuppressants have become the focus of current research. Activated T cells are important cells in mediating transplantation rejection. Selective clearance of activated T cells and retention of resting cells can control the occurrence of transplant rejection and reduce the toxic and side effects of drugs. The activated T cells expressed CTLA-4 molecules on the surface. Based on this, we designed the anti-CTLA-4 single chain antibody (scFv) as the directed fragment, and the pore forming molecule perforin perforinpore-forming protein (PFP) channel formation function domain was a killing fragment immunotoxin. To selectively remove activated T cells. The anti CTLA-4 antibody can selectively bind to activated T cells. Membrane pore morphogenetic protein (MMP) is used as an immunotoxin killing fragment, which overcomes the disadvantages of large toxicity, strong immunogenicity and low molecular internalization efficiency of the existing cytotoxic fragments. Become a more dominant killing fragment. In this study, anti-CTLA-4 single chain antibody (scFv) was used as the directed fragment and perforin pore was formed.
【学位授予单位】：四川大学
【学位级别】：博士
【学位授予年份】：2005
【分类号】：R392.1

【引证文献】