人粘蛋白1连续重复区基因疫苗肿瘤免疫的研究
发布时间：2018-08-06 15:48
【摘要】： 人粘蛋白1(MUC1)是一种肿瘤相关抗原(TAA)，其能够诱导细胞毒T淋巴细胞杀伤活性的表位肽主要集中在其可变数目连续重复区(VNTR)中，使MUC1 VNTR成为免疫治疗的潜在靶点。为研究MUC1 VNTR基因疫苗的特异性抗肿瘤作用，我们构建了含有人粘蛋白1连续重复区(MUC1 VNTR)序列的基因及其真核表达载体，建立了MUC1 VNTR稳定表达肿瘤细胞系和动物模型，探讨了MUC1 VNTR基因疫苗在小鼠体内诱导的免疫应答及白细胞介素-2(IL-2)表达质粒佐剂的免疫增强作用，并考察了MUC1 VNTR基因疫苗及IL-2质粒共免疫对模型小鼠肿瘤的免疫预防和治疗作用。MUC1 VNTR基因疫苗免疫小鼠后，，在小鼠体内成功诱导出MUC1 VNTR特异的细胞及体液免疫应答，而且细胞免疫反应强度随着VNTR重复区数目和免疫次数的增加、以及细胞因子质粒佐剂的作用而明显增强。MUC1 VNTR基因疫苗与IL-2质粒共免疫后，能够明显地预防和治疗表达MUC1(MUC1+)肿瘤细胞在小鼠体内的生长，与未免疫小鼠比较，荷瘤小鼠的生存期明显延长。MUC1 VNTR基因疫苗和IL-2质粒佐剂的联合应用，对MUC1相关肿瘤的免疫预防和治疗具有潜在价值。
[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.
【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】：R392
本文编号：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.
【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】：R392
【参考文献】
相关期刊论文 前2条
1 罗晨;李官成;;DNA疫苗与肿瘤免疫治疗[J];国际病理科学与临床杂志;2006年04期
2 台桂香,张吉凤,朱迅;重组人MUC1-MBP融合蛋白的抗肿瘤作用[J];中国肿瘤生物治疗杂志;2003年03期
本文编号：2168202
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