人粘蛋白1連續(xù)重復區(qū)基因疫苗腫瘤免疫的研究
發(fā)布時間：2018-08-06 15:48
【摘要】： 人粘蛋白1(MUC1)是一種腫瘤相關(guān)抗原(TAA)，其能夠誘導細胞毒T淋巴細胞殺傷活性的表位肽主要集中在其可變數(shù)目連續(xù)重復區(qū)(VNTR)中，使MUC1 VNTR成為免疫治療的潛在靶點。為研究MUC1 VNTR基因疫苗的特異性抗腫瘤作用，我們構(gòu)建了含有人粘蛋白1連續(xù)重復區(qū)(MUC1 VNTR)序列的基因及其真核表達載體，建立了MUC1 VNTR穩(wěn)定表達腫瘤細胞系和動物模型，探討了MUC1 VNTR基因疫苗在小鼠體內(nèi)誘導的免疫應答及白細胞介素-2(IL-2)表達質(zhì)粒佐劑的免疫增強作用，并考察了MUC1 VNTR基因疫苗及IL-2質(zhì)粒共免疫對模型小鼠腫瘤的免疫預防和治療作用。MUC1 VNTR基因疫苗免疫小鼠后，，在小鼠體內(nèi)成功誘導出MUC1 VNTR特異的細胞及體液免疫應答，而且細胞免疫反應強度隨著VNTR重復區(qū)數(shù)目和免疫次數(shù)的增加、以及細胞因子質(zhì)粒佐劑的作用而明顯增強。MUC1 VNTR基因疫苗與IL-2質(zhì)粒共免疫后，能夠明顯地預防和治療表達MUC1(MUC1+)腫瘤細胞在小鼠體內(nèi)的生長，與未免疫小鼠比較，荷瘤小鼠的生存期明顯延長。MUC1 VNTR基因疫苗和IL-2質(zhì)粒佐劑的聯(lián)合應用，對MUC1相關(guān)腫瘤的免疫預防和治療具有潛在價值。
[Abstract]:Human mucin 1 (MUC1) is a tumor-associated antigen (TAA), its epitope peptide which can induce cytotoxic T lymphocyte cytotoxicity is mainly concentrated in its variable number of continuous repeat region (VNTR) which makes MUC1 VNTR a potential target for immunotherapy. In order to study the specific antitumor effect of MUC1 VNTR gene vaccine, we constructed the gene containing human mucin 1 continuous repeat region (MUC1 VNTR) and its eukaryotic expression vector, and established the stable expression of MUC1 VNTR tumor cell line and animal model. The immune response induced by MUC1 VNTR gene vaccine in mice and the immune enhancement of interleukin-2 (IL-2) expression plasmid adjuvant were studied. The effects of MUC1 VNTR gene vaccine and IL-2 plasmid co-immunization on tumor prevention and treatment in model mice. MUC1 VNTR gene vaccine was used to immunize mice. The specific cellular and humoral immune responses of MUC1 VNTR were successfully induced in mice. Moreover, with the increase of the number of VNTR repeats and the number of immunizations, and the effect of cytokine plasmid adjuvant, the intensity of cellular immune response increased significantly after co-immunization with IL-2 plasmid. It can obviously prevent and treat the growth of tumor cells expressing MUC1 (MUC1) in mice. Compared with unimmunized mice, the survival time of tumor-bearing mice was significantly prolonged by the combination of MUC1 VNTR gene vaccine and IL-2 plasmid adjuvant. Immunoprophylaxis and treatment of MUC1 associated tumors have potential value.
【學位授予單位】：吉林大學
【學位級別】：博士
【學位授予年份】：2007
【分類號】：R392
本文編號：2168202
[Abstract]:Human mucin 1 (MUC1) is a tumor-associated antigen (TAA), its epitope peptide which can induce cytotoxic T lymphocyte cytotoxicity is mainly concentrated in its variable number of continuous repeat region (VNTR) which makes MUC1 VNTR a potential target for immunotherapy. In order to study the specific antitumor effect of MUC1 VNTR gene vaccine, we constructed the gene containing human mucin 1 continuous repeat region (MUC1 VNTR) and its eukaryotic expression vector, and established the stable expression of MUC1 VNTR tumor cell line and animal model. The immune response induced by MUC1 VNTR gene vaccine in mice and the immune enhancement of interleukin-2 (IL-2) expression plasmid adjuvant were studied. The effects of MUC1 VNTR gene vaccine and IL-2 plasmid co-immunization on tumor prevention and treatment in model mice. MUC1 VNTR gene vaccine was used to immunize mice. The specific cellular and humoral immune responses of MUC1 VNTR were successfully induced in mice. Moreover, with the increase of the number of VNTR repeats and the number of immunizations, and the effect of cytokine plasmid adjuvant, the intensity of cellular immune response increased significantly after co-immunization with IL-2 plasmid. It can obviously prevent and treat the growth of tumor cells expressing MUC1 (MUC1) in mice. Compared with unimmunized mice, the survival time of tumor-bearing mice was significantly prolonged by the combination of MUC1 VNTR gene vaccine and IL-2 plasmid adjuvant. Immunoprophylaxis and treatment of MUC1 associated tumors have potential value.
【學位授予單位】：吉林大學
【學位級別】：博士
【學位授予年份】：2007
【分類號】：R392
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相關(guān)期刊論文 前2條
1 羅晨;李官成;;DNA疫苗與腫瘤免疫治療[J];國際病理科學與臨床雜志;2006年04期
2 臺桂香,張吉鳳,朱迅;重組人MUC1-MBP融合蛋白的抗腫瘤作用[J];中國腫瘤生物治療雜志;2003年03期
本文編號：2168202
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