HSP65-MUC1通过分子模拟损伤小鼠胰腺的可能性研究

发布时间：2018-03-18 16:27

本文选题：HSP65-MUC1　切入点：通过　出处：《吉林大学》2007年博士论文　论文类型：学位论文

【摘要】： 卡介苗热休克蛋白65-MUC1多肽融合蛋白(HSP65-MUC1)是一种治疗肿瘤的重组蛋白疫苗,在进入树突状细胞(DCs)后,经MHCI类途径加工提呈,可激活MUC1特异性CTL去杀伤表达MUC1抗原的肿瘤。因为卡介苗热休克蛋白65(HSP65)和人体热休克蛋白60(HSP60)存在高度同源性,且人胰岛β细胞高表达HSP60,因此在应用HSP65-MUC1后可能通过分子模拟的方式诱导人体产生针对HSP60的交叉免疫应答,进而造成胰腺β细胞的破坏,引发自身免疫性糖尿病。为了证实HSP65-MUC1的安全性,采用正常小鼠和荷瘤小鼠,我们研究了HSP65-MUC1通过分子模拟损伤小鼠胰腺的可能性。结果表明:1、注射后的HSP65-MUC1未在胰腺大量滞留;2、HSP65-MUC1可在小鼠诱生HSP65特异性的细胞毒性T淋巴细胞(CTL);3、HSP65-MUC1诱生的HSP65特异性淋巴细胞能和小鼠的HSP(包括HSP60)发生交叉反应;4、反复注射HSP65-MUC1的小鼠未发生明显的胰腺损伤。本工作为HSP65-MUC1临床应用的安全性提供了重要参考。
[Abstract]:BCG heat shock protein 65-MUC1 polypeptide fusion protein HSP65-MUC1) is a recombinant protein vaccine for the treatment of tumor. After entering into dendritic cells (DCs), it is processed and presented by MHCI pathway, which can activate MUC1 specific CTL to kill the tumor expressing MUC1 antigen. Because of the high homology between HSP65 (HSP65) and HSP60 (human HSP60), and the high expression of HSP60 in human islet 尾 cells, the cross-immune response to HSP60 may be induced by molecular simulation after the application of HSP65-MUC1. In turn, the destruction of pancreatic 尾-cells, causing autoimmune diabetes. To verify the safety of HSP65-MUC1, normal mice and tumor-bearing mice were used. We studied the possibility that HSP65-MUC1 could damage the pancreas of mice by molecular simulation. The results showed that the injected HSP65-MUC1 did not remain in the pancreas in large quantities. HSP65-MUC1 could induce the HSP65 specificity of HSP65 specific cytotoxic T lymphocytes in mice. Lymphocytes could cross react with HSP60 of mice (including HSP60), but no obvious pancreatic injury occurred in mice injected repeatedly with HSP65-MUC1. This work provides an important reference for the safety of clinical application of HSP65-MUC1.
【学位授予单位】：吉林大学
【学位级别】：博士
【学位授予年份】：2007
【分类号】：R657.51;R392

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