热休克蛋白65-HER2多表位融合蛋白的构建及其生物学功能研究
发布时间：2018-10-17 20:41
【摘要】：乳腺癌是严重危害女性健康的恶性肿瘤。研究发现: HER2蛋白(HER2)的表达与乳腺癌的发生、转移和预后密切相关。正常情况下,HER2在乳腺上皮细胞和其他正常细胞有低水平表达。约有25-30%的乳腺癌患者的肿瘤细胞高水平表达HER2,此外,高表达HER2的乳腺癌患者易产生耐药性并多有不良的预后。因此,HER2可能成为乳腺癌免疫治疗的靶点。 结核分支杆菌热休克蛋白65(HSP65)具有分子伴侣及分子佐剂的作用。在抗肿瘤的免疫应答过程中,HSP65可激活机体的非特异性免疫系统,并可引导与其形成复合物或与之融合的抗原肽在树突状细胞内经MHCI类途径加工递呈,从而激活抗原特异性的细胞毒性T淋巴细胞( CTLs )。 我们将HSP65与HER2的表位肽基因相连接,并在大肠杆菌中成功地表达了热休克蛋白65-HER2多表位融合蛋白(HSP65-HER2)。获得纯化的HSP65-HER2后,我们研究了HSP65-HER2的生物学功能。人体外实验表明:经HSP65-HER2诱导的T淋巴细胞可通过特异性及非特异性的免疫机制抑制HER2阳性肿瘤细胞的生长。小鼠体内实验表明:HSP65-HER2能够诱导对HER2阳性肿瘤细胞的特异性杀伤。因此,HSP65-HER2可能成为一种对HER2阳性乳腺癌有预防或治疗价值的新的生物制剂。
[Abstract]:Breast cancer is a malignant tumor that seriously endangers the health of women. It is found that the expression of HER2 protein (HER2) is closely related to the occurrence, metastasis and prognosis of breast cancer. Under normal conditions, HER2 is expressed at low level in breast epithelial cells and other normal cells. About 25-30% of breast cancer patients expressed HER2, at high level. In addition, breast cancer patients with high expression of HER2 were prone to develop drug resistance and poor prognosis. Therefore, HER2 may be the target of immunotherapy for breast cancer. Mycobacterium tuberculosis heat shock protein 65 (HSP65) has molecular chaperone and molecular adjuvant. In the process of anti-tumor immune response, HSP65 can activate the body's non-specific immune system, and can lead to the formation of complex or fusion of antigenic peptides in dendritic cells via MHCI pathway. Thus activating antigen-specific cytotoxic T lymphocyte (CTLs). We linked HSP65 with the epitope peptide gene of HER2 and successfully expressed the heat shock protein 65-HER2 multiepitope fusion protein (HSP65-HER2) in Escherichia coli. After obtaining purified HSP65-HER2, we studied the biological function of HSP65-HER2. In vitro human body experiments showed that T lymphocytes induced by HSP65-HER2 could inhibit the growth of HER2 positive tumor cells through specific and non-specific immune mechanisms. In vivo experiments in mice showed that HSP65-HER2 could induce specific killing of HER2 positive tumor cells. Therefore, HSP65-HER2 may become a new biological agent with preventive or therapeutic value for HER2-positive breast cancer.
【学位授予单位】：吉林大学
【学位级别】：博士
【学位授予年份】：2006
【分类号】：R341
本文编号：2277907
[Abstract]:Breast cancer is a malignant tumor that seriously endangers the health of women. It is found that the expression of HER2 protein (HER2) is closely related to the occurrence, metastasis and prognosis of breast cancer. Under normal conditions, HER2 is expressed at low level in breast epithelial cells and other normal cells. About 25-30% of breast cancer patients expressed HER2, at high level. In addition, breast cancer patients with high expression of HER2 were prone to develop drug resistance and poor prognosis. Therefore, HER2 may be the target of immunotherapy for breast cancer. Mycobacterium tuberculosis heat shock protein 65 (HSP65) has molecular chaperone and molecular adjuvant. In the process of anti-tumor immune response, HSP65 can activate the body's non-specific immune system, and can lead to the formation of complex or fusion of antigenic peptides in dendritic cells via MHCI pathway. Thus activating antigen-specific cytotoxic T lymphocyte (CTLs). We linked HSP65 with the epitope peptide gene of HER2 and successfully expressed the heat shock protein 65-HER2 multiepitope fusion protein (HSP65-HER2) in Escherichia coli. After obtaining purified HSP65-HER2, we studied the biological function of HSP65-HER2. In vitro human body experiments showed that T lymphocytes induced by HSP65-HER2 could inhibit the growth of HER2 positive tumor cells through specific and non-specific immune mechanisms. In vivo experiments in mice showed that HSP65-HER2 could induce specific killing of HER2 positive tumor cells. Therefore, HSP65-HER2 may become a new biological agent with preventive or therapeutic value for HER2-positive breast cancer.
【学位授予单位】：吉林大学
【学位级别】：博士
【学位授予年份】：2006
【分类号】：R341
【参考文献】
相关期刊论文 前1条
1 李玉保,付旭彬,鲍恩东;热休克蛋白研究进展[J];畜牧与兽医;2004年11期
，本文编号：2277907
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