摘要
目的探讨自体肿瘤疫苗预防和治疗肝癌的效果及抗癌机制.方法采用多聚甲醛固定的小鼠Hepa1-6细胞为抗原、粒细胞-巨噬细胞集落刺激因子(GM-CSF)和白介素-2(IL-2)缓释微球为免疫激活剂、辅以免疫辅助剂TiterMax Gold的肝癌疫苗皮内接种C57BL/6J小鼠,观察肿瘤疫苗预防和治疗肝癌的效果.结果对照组15只小鼠全部发展成肝肿瘤;含有固定Hepa1-6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Hepa1-6细胞接种于左躯干皮下.肿瘤长至直径5 mm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 d,肿瘤生长受到抑制,随后明显缩小.60%小鼠的肿瘤完全消失.细胞毒性实验结果显示,接种疫苗的小鼠脾细胞的杀瘤活性可被抗-CD3+、抗-CD8+、抗-MHC-Ⅰ单克隆抗体所阻断,但不被抗-CD4+、抗-MHC-Ⅱ单克隆抗体所阻断.结论自体肿瘤疫苗具有很强的抗肿瘤的效果.其抗瘤机制是诱导内源性抗原特异性CTL反应,由典型的MHC-I限制的CD8+ T细胞所介导的.
Objective To investigate the role of autologous tumor vaccine for prevention and treatment of HCC and explore its anti-tumor mechanism. Methods The autologous tumor vaccine for HCC was developed by using fixed HCC cells as antigen, biodegradable microparticles encapsulating granulocyte-macrophage-colony stimulating factor （GM-CSF） and interleukin-2 （IL-2） as the immune activating agent and TiterMax Gold as the supplementing agent. Then the vaccine was intradermally inoculated into the C57BL/6J mice to investigate its role for prevention and treatment of HCC. Results All the 15 non-immunized mice developed HCC. The rate of protection in mice immunized with fixed Hepal-6 cells and both of IL-2/GM-CSF microsphere or further mixed with TiterMax Gold reached 80% and 87%, respectively. The established tumors of 5 mm in diameter was markedly reduced by vaccination twice and eventually resulted in complete regression in 60% of the mice. The tumors in control mice continued to grow. Cultured splenocytes from the vaccinated mice showed specific lysis of Hepal-6 target cells. The cytotoxic activity of vaccine was inhibited by the treatment with anti-CD3, anti-CD8 and anti-MHC-class Ⅰ monoclonal antibodies but not with anti-CD4 and anti-MHC-class Ⅱ antibodies. Conclusions Fixed HCC vaccination can elicit protective and therapeutic antitumor immunity against HCC. The mechanism of which might be that it can induce internal antigen-specific CTL response modulated by the typical MHC-class Ⅰ restricted CD8^＋ T cells.
出处
《中华肝胆外科杂志》
CAS
CSCD
2005年第8期551-554,共4页
Chinese Journal of Hepatobiliary Surgery
基金
广东千百十工程基金(Q校02010)
