Yoshiura Kenta, Nishishita Toshihide, Nakaoka Takashi, Yamashita Naohide, Yamashita Naomi
Research Institute of Pharmaceutical Sciences, Musashino University, Shinmachi 1-1-20, Nishitokyo-shi, Tokyo 202-8585, Japan.
J Exp Clin Cancer Res. 2009 Jan 31;28(1):13. doi: 10.1186/1756-9966-28-13.
Key role of angiogenesis in tumor growth and metastasis based on accumulating evidence and recent progress of immunotherapy have led us to investigate vaccine therapy targeting tumor angiogenesis.
C57BL/6J mice were vaccinated with a syngeneic endothelial cell line Tpit/E by subcutaneous injection once a week. Prior to ninth vaccination, the mice were challenged with B16/F10 melanoma cells by subcutaneous inoculation on the back for the tumor growth model or by tail venous injection for the lung metastasis model. Development of subcutaneous tumor and lung metastasis was monitored by computed tomography scanning, which enabled accurate evaluation with the minimized sacrifice of mice.
Vaccination with Tpit/E cells inhibited subcutaneous tumor growth and appearance of lung metastasis compared to control. Survival period was elongated in the Tpit/E vaccination in both of the two models. We also obtained hybridomas secreting specific antibodies to Tpit/E cells from a mouse vaccinated with the cells, indicating that specific immune response to the syngeneic endothelial cells was elicited.
These results suggest that vaccination with an autologous endothelial cell line may be effective against melanoma.
基于越来越多的证据以及免疫疗法的最新进展,血管生成在肿瘤生长和转移中起着关键作用,这促使我们研究针对肿瘤血管生成的疫苗疗法。
C57BL/6J小鼠每周皮下注射一次同基因内皮细胞系Tpit/E进行疫苗接种。在第九次接种前,通过在背部皮下接种B16/F10黑色素瘤细胞建立肿瘤生长模型,或通过尾静脉注射建立肺转移模型。通过计算机断层扫描监测皮下肿瘤和肺转移的发展情况,这样能够在尽量减少小鼠牺牲数量的情况下进行准确评估。
与对照组相比,接种Tpit/E细胞可抑制皮下肿瘤生长和肺转移的出现。在两种模型中,接种Tpit/E细胞均延长了生存期。我们还从接种该细胞的小鼠中获得了分泌针对Tpit/E细胞特异性抗体的杂交瘤,这表明引发了针对同基因内皮细胞的特异性免疫反应。
这些结果表明,用自体内皮细胞系进行疫苗接种可能对黑色素瘤有效。