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[通过肿瘤细胞与树突状细胞的基因工程融合诱导针对肿瘤的Th1免疫反应]

[Induction of Th1 immune response against tumor by genetically engineered fusion of tumor cells and dendritic cells].

作者信息

Zhang Weidong, Yang Hong, Zeng Hongtao, Chen Zhuang

机构信息

Department of Microbiology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.

出版信息

Zhonghua Xue Ye Xue Za Zhi. 2002 Feb;23(2):61-4.

Abstract

OBJECTIVE

To study the antitumor activity of engineered fusion of tumor cell and dendritic cells (DC).

METHODS

J558 tumor cells were transfected with mouse IL-12 (mIL-12) gene and then fused with DCs to develop a hybrid-engineered tumor vaccine. BALB/c mice were challenged with wild-type J558 tumor cells 14 days after vaccinated with hybrid-engineered J558.

RESULTS

mIL-12 was detected at (870 +/- 60) pg.(10(5) cells)(-1).ml(-1) in the culture supernatants and the cell-fusion rate was about 30% by co-focal microscopy. In addition, the lymphocytes from popliteal nodes and groin nodes of these mice vaccinated with hybrid-engineered J558 secreted higher levels of IFN-gamma than that of other control mice, and vaccination of mice with the fusion vaccine induced more efficient tumor-specific CTL cytotoxicity against wild-type tumor cells in vitro and with efficient antitumor immunity in vivo.

CONCLUSION

It suggested that vaccination of mice with the fusion vaccine induced stronger Th1-dominant responses and this approach could perhaps be applied to clinical settings of DCs-based cancer vaccines.

摘要

目的

研究肿瘤细胞与树突状细胞(DC)工程融合体的抗肿瘤活性。

方法

用小鼠白细胞介素-12(mIL-12)基因转染J558肿瘤细胞,然后与DC融合以制备杂交工程化肿瘤疫苗。用杂交工程化J558疫苗接种BALB/c小鼠14天后,用野生型J558肿瘤细胞攻击。

结果

培养上清中mIL-12的检测浓度为(870±60)pg·(10⁵细胞)⁻¹·ml⁻¹,共聚焦显微镜检测细胞融合率约为30%。此外,用杂交工程化J558疫苗接种的小鼠腘窝淋巴结和腹股沟淋巴结中的淋巴细胞分泌的γ干扰素水平高于其他对照小鼠,用融合疫苗接种小鼠在体外诱导了对野生型肿瘤细胞更有效的肿瘤特异性CTL细胞毒性,并在体内诱导了有效的抗肿瘤免疫。

结论

提示用融合疫苗接种小鼠可诱导更强的以Th1为主的反应,这种方法可能适用于基于DC的癌症疫苗的临床应用。

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