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目的 探讨采用细胞因子缓释微球的肿瘤疫苗预防和治疗肝癌的疗效及抗癌机制。方法 我们研制开发了一种肿瘤疫苗,其组成是固定的肿瘤细胞或组织碎片、细胞因子缓释微球和免疫辅助药。采用多聚甲醛固定的小鼠Hepal-6细胞或肿瘤碎片、微球包装的GM-CSF和/IL-2和合成TiterMax Gold等不同成份的瘤苗皮内接种C57BL/6J小鼠,随后肝内接种活体Hepal-6细胞。结果 对照组15只小鼠全部发展成肝肿瘤;含有固定Hepal-6细胞和IL-2及GM-CSF微球的肿瘤疫苗,80％小鼠获得保护。再加入免疫辅助剂TiterMax Gold的肿瘤疫苗,则87％小鼠获得保护。将Hepal-6细胞接种于左躯干皮下。肿瘤长至直径5mm时,皮内接种肿瘤疫苗2次。结果显示,对照组肿瘤继续生长。疫苗组在第2次接种后7-10天,10只小鼠中9只肿瘤生长受到抑制,随后明显缩小。60％小鼠的肿瘤完全消散。细胞毒性实验结果显示,未接种疫苗的小鼠脾细胞不能杀灭Hepal-6细胞和其他肿瘤细胞;而接种疫苗的小鼠脾细胞对Hepal-6细胞杀瘤活性达41％,但对B16-F1,Lewis肺癌细胞(LLC),肾癌细胞(Renca),膀胱癌细胞(MBT-2)则无效。疫苗的Ⅰ期临床实验结果显示肝癌疫苗能有效地预防肝癌术后复发,诱导DTH反应。结论 肝癌疫苗能有效预防和治疗原发性肝癌,其抗瘤机制是诱导内源性抗原特异性CTL反?
Objective To investigate the efficacy and anticancer mechanism of tumor vaccine with cytokine sustained-release microspheres in the prevention and treatment of liver cancer. Methods We developed a tumor vaccine consisting of fixed tumor cells or tissue fragments, cytokine release microspheres and immune adjuvants. C57BL / 6J mice were inoculated intradermally with paraformaldehyde-fixed mouse Hepal-6 cells or tumor fragments, microsphere-encapsulated GM-CSF and / IL-2 and synthetic TiterMax Gold, In vivo Hepal-6 cells were seeded. Results All 15 mice in the control group developed liver tumors. Tumor vaccines containing Hepal-6 cells and IL-2 and GM-CSF microspheres were fixed in 80% of the mice. Tumor vaccines, supplemented with the adjuvant TiterMax Gold, were then protected in 87% of mice. Hepal-6 cells were seeded subcutaneously into the left trunk. When the tumor grew to 5mm in diameter, the tumor vaccine was inoculated twice in the skin. The results showed that the control group tumors continue to grow. In the vaccine group, 7 to 10 days after the second vaccination, the growth of 9 of 10 mice was inhibited and then significantly reduced. Tumors in 60% of mice completely dissipated. The results of cytotoxicity showed that unvaccinated mouse spleen cells could not kill Hepal-6 cells and other tumor cells; while the vaccination of mice spleen cells on Hepal-6 cell killing activity of 41%, but the B16- F1, Lewis lung cancer cells (LLC), Renca cells and bladder cancer cells (MBT-2) are ineffective. Phase I clinical trials of vaccine showed that HCC vaccine can effectively prevent postoperative recurrence of liver cancer and induce DTH reaction. Conclusion Hepatoma vaccine can effectively prevent and treat primary hepatocellular carcinoma and its anti-tumor mechanism is to induce endogenous antigen-specific CTL reaction.