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β-榄香烯联合白细胞介素-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 of beta-elemene combined with interleukin-23 gene-modified dendritic cells on murine pancreatic carcinoma].

作者信息

Tan Guang, Wang Zhong-Yu, Wang Xiao-Gang, Cheng Lei, Yin Shuo

机构信息

Department of General Surgery, The First Affiliated Hospital, Dalian Medical University, Dalian, Liaoning, 116011, P. R. China.

出版信息

Ai Zheng. 2006 Sep;25(9):1082-6.

Abstract

BACKGROUND & OBJECTIVE: Dendritic cell (DC) vaccine is a kind of treatment vaccine with clinical application potency. Functional cytokines can enhance anti-tumor immune response of dendritic cells. This study was to investigate the protective effects on murine pancreatic carcinoma by beta-elemene combined with bone marrow-derived dendritic cells (BM-DCs) modified with murine interleukin (IL)-23 gene.

METHODS

The murine IL-23 cDNA was sub-cloned into dual-expression vector. DCs were pulsed with tumor cell lysate after modified by IL-23 gene. Mice were injected with IL-23-transfected DC vaccine, non-transfected DC vaccine, and sodium, respectively. The immune preventative and immunotherapeutic effects of DC vaccines on mice and the cytokine release in vivo were assessed. Effects of vaccine combined with beta-elemene on tumor growth and survival period of the mice were observed.

RESULTS

IL-23 protein apparently increased the antigen-presenting ability of DCs. After the vaccination of DC vaccines, IFN-gamma production in treatment group was significantly more than that of the control group (P<0.01), as well as, IL-4 production was less than that in the normal group (P<0.05). Tumor growth was obviously inhibited and the survival period of the mice was obviously prolonged in beta-elemene combined with DC vaccine group than in DC, beta-elemene, or control group (P<0.01).

CONCLUSIONS

IL-23-modified DC vaccines can enhance specific Th1-type and CTL response against pancreatic carcinoma cells, induce not only preventative immunity, but also auto-immunity against pancreatic carcinoma. Moreover, beta-elemene has great collaborative anti-tumor function.

摘要

背景与目的

树突状细胞(DC)疫苗是一种具有临床应用潜力的治疗性疫苗。功能性细胞因子可增强树突状细胞的抗肿瘤免疫反应。本研究旨在探讨β-榄香烯联合经小鼠白细胞介素(IL)-23基因修饰的骨髓源性树突状细胞(BM-DCs)对小鼠胰腺癌的保护作用。

方法

将小鼠IL-23 cDNA亚克隆至双表达载体。IL-23基因修饰后的DC用肿瘤细胞裂解物脉冲处理。分别给小鼠注射IL-23转染的DC疫苗、未转染的DC疫苗和生理盐水。评估DC疫苗对小鼠的免疫预防和免疫治疗效果以及体内细胞因子的释放。观察疫苗联合β-榄香烯对小鼠肿瘤生长和生存期的影响。

结果

IL-23蛋白明显增强了DC的抗原呈递能力。接种DC疫苗后,治疗组IFN-γ的产生明显多于对照组(P<0.01),同时,IL-4的产生低于正常组(P<0.05)。β-榄香烯联合DC疫苗组小鼠的肿瘤生长明显受到抑制,生存期明显延长,优于DC组、β-榄香烯组或对照组(P<0.01)。

结论

IL-23修饰的DC疫苗可增强针对胰腺癌细胞的特异性Th1型和CTL反应,不仅诱导预防免疫,还诱导针对胰腺癌的自身免疫。此外,β-榄香烯具有强大的协同抗肿瘤作用。

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