Institute of Biotherapy, School of Biotechnology, Southern Medical University, Guangzhou, China.
Vaccine. 2010 Jul 12;28(31):4937-44. doi: 10.1016/j.vaccine.2010.05.038.
A novel therapeutic vaccine against prostate cancer was developed by simultaneous immobilization of streptavidin-tagged bioactive GM-CSF and TNFalpha on the biotinylated surface of 30% ethanol-fixed RM-1 prostatic cancer cells. This study showed that the GM-CSF/TNFalpha-doubly surface-modified vaccine significantly extended the survival in the orthotopic model of RM-1 prostate cancer, and was superior to single GM-CSF- or TNFalpha-surface-modified vaccine. Moreover, the splenocytes from the GM-CSF/TNFalpha-vaccine-treated mice showed the most potent cytotoxicity on RM-1 cells and the highest production of RM-1-specific IFNgamma. In addition, more CD4+ and CD8+ T cells infiltrated into the tumor sites in the GM-CSF/TNFalpha-vaccine-treated mice than in the GM-CSF- or TNFalpha-vaccine-treated mice. Therefore, our study demonstrated that the efficacy of RM-1 prostate cancer cell vaccine could be improved by conjugating both GM-CSF and TNFalpha simultaneously on the surface of cancer cells, and that this modification thus has a potential translational significance.
一种新型的治疗前列腺癌的治疗性疫苗是通过将链霉亲和素标记的生物活性 GM-CSF 和 TNFalpha 同时固定在生物素化的 30%乙醇固定的 RM-1 前列腺癌细胞表面上而开发的。本研究表明,GM-CSF/TNFalpha 双重表面修饰的疫苗可显著延长 RM-1 前列腺癌的原位模型中的存活时间,并且优于单独的 GM-CSF 或 TNFalpha 表面修饰的疫苗。此外,来自 GM-CSF/TNFalpha 疫苗治疗的小鼠的脾细胞对 RM-1 细胞表现出最强的细胞毒性和最高的 RM-1 特异性 IFNgamma 产生。此外,与 GM-CSF 或 TNFalpha 疫苗治疗的小鼠相比,GM-CSF/TNFalpha 疫苗治疗的小鼠的肿瘤部位有更多的 CD4+和 CD8+ T 细胞浸润。因此,我们的研究表明,通过将 GM-CSF 和 TNFalpha 同时结合到癌细胞表面上,可以提高 RM-1 前列腺癌细胞疫苗的疗效,并且这种修饰具有潜在的转化意义。