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β-榄香烯联合白介素-23基因修饰树突状细胞对小鼠胰腺癌的免疫治疗作用

Immunotherapeutic effects on murine pancreatic carcinoma by β-elemene combined with dendritic cells modified with genes encoding interleukin-23.

作者信息

Tan Guang, Wang Zhongyu, Che Luanqing, Yin Shuo

机构信息

Department of General Surgery, First Affiliated Hospital, Dalian Medical University, Dalian, 116011, China,

出版信息

Front Med China. 2007 Feb;1(1):41-5. doi: 10.1007/s11684-007-0008-4.

Abstract

The dendritic cell vaccine is a treatment vaccine with potent clinical applications. Functional cytokines can enhance dendritic cell anti-tumor immune responses. This experiment was conducted to study the effects of bone marrow-derived dendritic cells (BM-DCs) modified with genes encoding murine interleukin-23 (IL-23) on murine pancreatic carcinoma, and effects of the treatment of pancreatic carcinoma with β-elemene combined with IL-23-modified dendritic cell vaccine. The murine IL-23 cDNA was sub-cloned into a dual-expression vector. DCs were pulsed with tumor cell lysate after being modified wth IL-23. Mice were divided into groups which were injected with IL-23-transduced DC vaccine, non-transduced DC vaccine and sodium respectively. The preventive immune and immunotherapeutic effects of DC vaccines on mice and cytokine release in vivo were then assessed. Results showed inhibitory effects on tumor cells and increased survival time in the experimental group treated with the vaccine combined with β-elemene. The IL-23 protein apparently increases the antigen presenting ability of DCs. After injection with DC vaccines, IFN-γ production in the treatment group was significantly increased as compared with that in the control group (P<0.01), and IL-4 production was decreased as compared with that in the control group (P<0.05). Tumor size was obviously reduced, and survival time clearly prolonged in the group with β-elemene combined with DC vaccine, in comparison to the other treatment groups and the control (P<0.01). IL-23-modified dendritic cell vaccines enhance specific Th1-type and cytotoxic T lymphocyte (CTL) responses against pancreatic carcinoma cells, and induce not only auto-immune ability but also preventive immunity against pancreatic carcinoma implanted in mice. β-elemene has great anti-tumor collaborative functions.

摘要

树突状细胞疫苗是一种具有强大临床应用价值的治疗性疫苗。功能性细胞因子可增强树突状细胞的抗肿瘤免疫反应。本实验旨在研究用编码小鼠白细胞介素-23(IL-23)的基因修饰的骨髓源性树突状细胞(BM-DCs)对小鼠胰腺癌的影响,以及β-榄香烯联合IL-23修饰的树突状细胞疫苗治疗胰腺癌的效果。将小鼠IL-23 cDNA亚克隆到双表达载体中。用IL-23修饰后的树突状细胞用肿瘤细胞裂解物进行脉冲处理。将小鼠分为分别注射IL-23转导的树突状细胞疫苗、未转导的树突状细胞疫苗和生理盐水的组。然后评估树突状细胞疫苗对小鼠的预防性免疫和免疫治疗效果以及体内细胞因子的释放情况。结果显示,在联合β-榄香烯的疫苗治疗的实验组中,对肿瘤细胞有抑制作用且生存时间延长。IL-23蛋白明显增强了树突状细胞的抗原呈递能力。注射树突状细胞疫苗后,治疗组的IFN-γ产生量与对照组相比显著增加(P<0.01),IL-4产生量与对照组相比降低(P<0.05)。与其他治疗组和对照组相比,β-榄香烯联合树突状细胞疫苗组的肿瘤大小明显减小,生存时间明显延长(P<0.01)。IL-23修饰的树突状细胞疫苗增强了针对胰腺癌细胞的特异性Th1型和细胞毒性T淋巴细胞(CTL)反应,不仅诱导了自身免疫能力,还诱导了对植入小鼠体内的胰腺癌的预防性免疫。β-榄香烯具有强大的抗肿瘤协同作用。

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