项目名称： Hyper-IL-15通过增强肿瘤抗原特异的CD8+T细胞的功能杀伤肝癌细胞

项目编号： No.81502468

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 杜雪相

作者单位： 郑州大学

项目金额： 16.5万元

中文摘要： 肝癌属于高发生率和高死亡率的恶性肿瘤，免疫治疗带来新的希望。CD8+T细胞是主要的抗肿瘤免疫细胞，如何增强其功能是肝癌免疫治疗的关键。白细胞介素-15（IL-15）可以有效促进CD8+T细胞的扩增和功能，而IL-15与受体IL-15Rα形成融合蛋白hyperIL-15后可显著增强其功能。我们前期动物实验表明hyper IL-15能够打破肿瘤免疫耐受，优先激活和扩增肿瘤抗原特异性CD8+T细胞，有效抑制肝癌。我们正在构建和纯化人hyperIL-15融合蛋白，计划取得肝癌临床标本分离外周血单个核细胞（PBMC）、肿瘤浸润淋巴细胞(TIL)，在体外培养过程中分别加入hyperIL-15、IL-15及hIgG蛋白，比较三组细胞组成比例、数量和功能（细胞因子分泌，对自体原代肝癌细胞系杀伤等）的区别，希望hyperIL-15能够大量增加CD8+T细胞的数量和功能，更好的治疗肝癌。

中文关键词： 白细胞介素15；肝癌；CD8阳性T细胞；免疫治疗

英文摘要： Liver cancer is a high incidence and high mortality of cancer, immunotheraphy brings new hope. CD8+ T cells are the main effector cells of anti-tumor immunity.Thus,how to enhance their effector function will be the key for the treatment of liver cancer. Interleukin-15 (IL-15) promotes the proliferation and effector functions of CD8+T cells The function of IL-15 can be dramatically increased by attaching this cytokine to its soluble receptor IL-15Ra（sIL-15Ra）as a fusion protein which was recognized as an IL-15 superagonist(hyper-IL-15). Previous animal experiments showed that murine hyper IL-15 can break the immune tolerance, prior to activate and amplify tumor specific CD8 +T cells, effectively restrain the cancer liver. We are constructing and purificating humanized hyperIL-15 fusion protein, and plan to get liver cancer clinical specimens to isolate peripheral blood mononuclear cell (PBMC),tumor infiltrating lymphocytes (TIL), we will add hyperIL-15, IL-15 and hIgG protein in the process of in vitro culture, then detect the proportion , the number and function (secretion of cytokines, killing of autologous liver cancer cell line, etc.) of culture group in three groups, prospect that hyperIL - 15 can increase the number and function of CD8 + T cells to treat the liver cancer better.

英文关键词： IL-15;liver cancer;CD8+ T cells;immunotherapy