hBIOT2，一个新的CT抗原的鉴定和抗肿瘤功能研究

项目名称： hBIOT2，一个新的CT抗原的鉴定和抗肿瘤功能研究

项目编号： No.30801048

项目类型： 青年科学基金项目

立项/批准年度： 2009

项目学科： 医药、卫生

项目作者： 王春婷

作者单位： 四川大学

项目金额： 20万元

中文摘要： 我们前期研究发现新基因hBIOT2 在mRNA水平的表达具有睾丸特异性，在婴儿期和成人期分布有差异，在妇科肿瘤细胞株如内膜癌细胞株HEC-1A、宫颈癌细胞株Hela、Siha 和卵巢癌细胞株SKOV3有表达，提示hBIOT2可能参与细胞的成熟和分化过程、与恶性肿瘤的发生和演进相关，可能是一个新的CT抗原。本研究中RT-PCR检测了肺癌组织、鼻咽癌组织、肝癌组织等癌组织中hBIOT2的表达水平，结合组织芯片结果确定肺癌组织和鼻咽癌组织为hBIOT2高表达肿瘤类型。免疫组化进一步证实hBIOT2在癌组织中表达显著高于癌旁组织，且呈现肿瘤组织分化程度越低表达量越高的趋势。同时，我们以小鼠Lewis肺癌模型进行mBIOT2保护性疫苗抗肿瘤试验，结果显示疫苗组小鼠肿瘤生长显著减慢、荷瘤鼠生存期明显延长、具有显著的抗肿瘤作用。脾细胞过继试验、Cr51释放试验、CD4-/-、CD8-/-小鼠试验提示mBIOT2主要是通过CD8+ T细胞发挥抗肿瘤免疫反应。这些结果对于更好认识新抗原分子hBIOT2奠定了良好的试验基础。

中文关键词： 新基因功能；CT抗原；肿瘤免疫

英文摘要： In the prior studies, we found that hBIOT2 was only detected in the testes and distributed differently in infancy and adulthood. It was also expressed in some types of gynecological cancer cell lines such as HEC-1A、Hela、Siha and SKOV3, which suggested that as a new CT-antigen, hBIOT2 may be involved in cell maturation and differentiation process, and progression of malignant tumors. In this studies, hBIOT2 was detected in lung cancer, nasopharyngeal carcinoma tissue, liver cancer tissues and other cancer tissues with RT-PCR. Lung cancer and nasopharyngeal carcinoma were identified as objects in the later work. The immunohistochemical techniques were further confirmed that hBIOT2 in cancer tissues was significantly higher than the adjacent tissues, and presented the lower histological grades, the higher the amount. At the same time, mice with Lewis lung cancer were treated with mBIOT2 vaccine. The results showed that tumor growth of the vaccine group was significantly slowed down, survival was prolonged significantly. Adoptive transfer of splenocytes and depletion of immune cell subsets revealed that CD8+ T lymphocytes responses mediated tumor inhibition. These results contribute to better understanding of the new antigen molecules hBIOT2.

英文关键词： New gene function;CT antigen;anti-tumor immunity