[关键词]
[摘要]
目的:研究锚定表达GM-CSF的小鼠黑色素瘤作为肿瘤疫苗的有效性。方法:GM-CSF基因嵌合GPI信号肽修饰序列实现在B16小鼠黑色素瘤细胞表面的锚定表达,研究锚定修饰的B16细胞于同源C57BL/6小鼠的成瘤性及诱导抗肿瘤免疫的效果。结果:抑瘤实验结果表明,锚定修饰GM-CSF的肿瘤细胞免疫原性增强,成瘤性明显下降;成瘤率为58.8%,而肿瘤对照组为100%。活瘤苗接种实验结果显示锚定修饰的肿瘤细胞可以预防肿瘤的发生,肿瘤发生率仅为20%,说明抗肿瘤的免疫应答有记忆性,能够有效地防止野生型肿瘤细胞的攻击。结论:锚定修饰GM-CSF的肿瘤细胞可以诱导抗特异性的抗肿瘤反应,这种设计可以应用于肿瘤疫苗的研究中。
[Key word]
[Abstract]
Objective:To investigate the vaccine potency of GM-CSF anchored B16 tumor cells. Methods:In this study, mGM-CSF was expressed on surface of B16 mice melanoma cells by GPI-modifying. C57BL/6 mice were inoculated with GM-CSF anchored cells and wide-type B16 cells to evaluate whether the GM-CSF anchored cells could elicit a protective and systemtic antitumor response. Results:GM-CSF anchored cells resulted in remarkable loss of tumorgenicity in syngenetic mice. The tumor occurrence rate of GM-CSF anchored B16 cells was 58.8% on C57BL/6 mice with 1×10 6- B16 cells/mice inoculated (n=12) and that of wide-type B16 cells was 100%, The C57BL/6 mice receiving inoculation with 5×10 5 GM-CSF anchored cells/mice never grew tumor. These mice were challenged with wide-type B16 cells, and only a minority of mice grew tumor after wide-type B16 cells inoculation. Conclusion: GM-CSF protein anchored cells could elicit a protective and systemtic antitumor responses.
[中图分类号]
R737.9
[基金项目]
863计划项目(2001AA217131)资助