發(fā)布時間：2018-06-07 00:26

  本文選題：重組免疫毒素 + CTLA-4　； 參考：《四川大學(xué)》2005年博士論文

【摘要】：免疫抑制劑廣泛應(yīng)用于臨床,降低了急性排斥反應(yīng)的發(fā)生率,使移植受者的長期與近期存活率都有所提高,然而免疫抑制劑長期蓄積的毒副作用導(dǎo)致慢性藥物性損傷,制約了長期存活率的進一步提高。在供器官嚴重短缺的情況下,如何有效抑制排斥反應(yīng),保證移植物長期有功能存活、改善受者生活質(zhì)量是器官移植領(lǐng)域亟待解決的問題。尋求更加高效、低毒、低感染、低致瘤危險性的特異性免疫抑制劑已成為當前研究的重點。 活化T細胞是介導(dǎo)移植排斥的重要細胞,選擇性清除活化T細胞而保留靜息細胞,能控制移植排斥反應(yīng)發(fā)生,減少藥物的毒副作用�；罨疶細胞表面誘導(dǎo)性表達CTLA-4分子,基于此,我們設(shè)計以anti-CTLA-4單鏈抗體(scFv)為導(dǎo)向片段、膜孔道形成分子一穿孔素(perforin,pore-forming protein, PFP)孔道形成功能域為殺傷片段的免疫毒素,以選擇性清除活化的T細胞�？笴TLA-4抗體能選擇性地與活化T細胞結(jié)合,膜孔道形成蛋白作為免疫毒素殺傷片段,克服了現(xiàn)有胞內(nèi)作用殺傷片段毒副作用大、免疫原性強、分子內(nèi)化效率低的缺點,成為更具優(yōu)勢的殺傷片段。 本研究以anti-CTLA-4單鏈抗體(scFv)為導(dǎo)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.
【學(xué)位授予單位】：四川大學(xué)
【學(xué)位級別】：博士
【學(xué)位授予年份】：2005
【分類號】：R392.1

【引證文獻】

相關(guān)期刊論文 前1條

1 許培芳;何俊蓉;吳潔;李萍;閻文昭;;單鏈抗體hs83基因植物表達載體的構(gòu)建[J];西南農(nóng)業(yè)學(xué)報;2008年01期

相關(guān)碩士學(xué)位論文 前1條

1 陳利弘;人源化抗CTLA-4單鏈抗體及其免疫毒素融合蛋白的表達與純化研究：原核大腸桿菌與真核畢赤酵母表達系統(tǒng)[D];四川大學(xué);2006年

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本文編號：1988823