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用携带截短 neu 基因慢病毒修饰的单个低剂量树突状细胞可以有效抑制 neu 过表达肿瘤。

A single low dose of dendritic cells modified with lentivirus containing a truncated neu gene can effectively suppress neu-overexpressing tumors.

机构信息

Institute of Human Reproduction and Stem Cell Engineering, Central South University, National Engineering and Research Center of Human Stem Cell, Changsha, China.

出版信息

J Gene Med. 2010 Jul;12(7):604-12. doi: 10.1002/jgm.1475.

DOI:10.1002/jgm.1475
PMID:20533530
Abstract

BACKGROUND

Several types of viral-transduced HER2/neu-modified dendritic cells (DC(HER2/neu)) have been used for preventing and/or treating HER2/neu-overexpressing tumors. However, to date, lentivirus has not been used to generate HER2/neu-modified DCs.

METHODS

In the present study, we used recombinant lentivirus containing a truncated neu gene (rLVneu) to transduce murine bone marrow-derived dendritic cells and investigated their preventive and therapeutic effects on HER2/neu-overexpressing tumors.

RESULTS

The data obtained show that a single low dose of lentiviral-transduced DC(HER2/neu) could significantly elevate serum anti-neu antibody level, stimulate the proliferation of CD4 and CD8 T lymphocytes and interferon-gamma secretion, induce a long lasting preventive effect against HER2/neu-overexpressing tumors and significantly suppress the growth of established HER2/neu-overexpressing tumors.

CONCLUSIONS

The present study demonstrates that a single low dose of DCs modified with rLV containing a truncated neu oncogene can achieve a strong and long lasting effect on neu-overexpressing tumors, suggesting the possible clinical application of this strategy.

摘要

背景

已经有几种类型的经病毒转导的 HER2/neu 修饰树突状细胞(DC(HER2/neu))被用于预防和/或治疗 HER2/neu 过表达肿瘤。然而,迄今为止,尚未使用慢病毒来产生 HER2/neu 修饰的 DC。

方法

在本研究中,我们使用含有截短 neu 基因的重组慢病毒(rLVneu)转导鼠骨髓来源的树突状细胞,并研究其对 HER2/neu 过表达肿瘤的预防和治疗作用。

结果

获得的数据表明,单次低剂量的慢病毒转导的 DC(HER2/neu)可显著提高血清抗 neu 抗体水平,刺激 CD4 和 CD8 T 淋巴细胞的增殖和干扰素-γ的分泌,诱导针对 HER2/neu 过表达肿瘤的长期预防作用,并显著抑制已建立的 HER2/neu 过表达肿瘤的生长。

结论

本研究表明,单次低剂量的用含有截短 neu 癌基因的 rLV 修饰的 DC 可对 neu 过表达肿瘤产生强烈和持久的作用,提示该策略可能具有临床应用前景。

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