Tumor vaccine therapy against recrudescent tumor using dendritic cells simultaneously transfected with tumor RNA and granulocyte macrophage colony-stimulating factor RNA
Tumor vaccine therapy against recrudescent tumor using dendritic cells simultaneously transfected with tumor RNA and granulocyte macrophage colony-stimulating factor RNA
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DOI：
10.1111/j.1349-7006.2007.00698.x
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发表时间：
2008-02-01
期刊：
影响因子：
5.7
通讯作者：
Yamaue, Hiroki
中科院分区：
文献类型：
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作者：
Naka, Teiji;Iwahashi, Makoto;Yamaue, Hiroki
最近，用肿瘤RNA转染的树突状细胞（DC）已被用作癌症疫苗。检查使用DC转染的肿瘤RNA的癌症疫苗的功效。特别令人感兴趣的是，使用用复发肿瘤RNA转染的DC的疫苗是否有效治疗先前免疫治疗后的再生长肿瘤。此外，检查了粒细胞巨噬细胞集落刺激因子（GM-CSF）mRNA的共转染以增强DC疫苗的有用性。将携带CT 26肿瘤的小鼠通过s.c.注射用CT 26 mRNA转染的DC（DC-CT 26）。DC-CT 26免疫小鼠对CT 26的细胞毒活性显著高于对照组（P < 0.001），GM-CSF mRNA共转染增强了DC-CT 26免疫小鼠对CT 26的细胞毒活性（P < 0.05），使DC-CT 26皮下注射对CT 26的治疗效果显著。肿瘤模型转染复发肿瘤mRNA的DC疫苗诱导的细胞毒性T淋巴细胞对复发的CT 26肿瘤细胞具有较强的杀伤活性，明显高于DC-CT 26疫苗诱导的细胞毒性T淋巴细胞（P < 0.05）。此外，在复发肿瘤模型中，该疫苗接种抑制了s.c. GM-CSFmRNA共转染组对肿瘤细胞的杀伤作用明显增强（P < 0.05）。这些结果表明，使用同时转染全肿瘤RNA和GM-CSF mRNA的DC的疫苗接种治疗可以产生治疗性免疫应答，即使是针对先前疫苗接种后的复发肿瘤。
Recently, dendritic cells (DC) transfected with tumor RNA have been used as a cancer vaccine. The efficacy of a cancer vaccine using DC transfected tumor RNA was examined. Of particular interest was whether a vaccine using DC transfected with recrudescent tumor RNA is effective for the treatment of a regrowing tumor after prior immunotherapy. In addition, the usefulness of co-transfection of granulocyte macrophage colony-stimulating factor (GM-CSF) mRNA to augment the DC vaccine was examined. CT26 tumor-bearing mice were immunized by s.c. injection with DC transfected with CT26 mRNA (DC-CT26). The cytotoxic activity against CT26 in mice immunized with DC-CT26 was significantly higher than that in the control group (P < 0.001) and was augmented by GM-CSF mRNA co-transfection (P < 0.05), resulting in remarkable therapeutic efficacy in CT26 s.c. tumor models. Cytotoxic T lymphocytes induced by the vaccination using DC transfected with mRNA from the recrudescent tumor showed a potent cytotoxicity against the recrudescent CT26 tumor cells, which was significantly higher than the cytotoxicity induced by the vaccination using DC-CT26 (P < 0.05). In addition, in a recrudescent tumor model, this vaccination suppressed the regrowing s.c. tumors, and was augmented by GM-CSF mRNA co-transfection (P < 0.05). These results suggested that vaccination therapy using DC simultaneously transfected with whole tumor RNA and GM-CSF mRNA could generate therapeutic immune responses even against recrudescent tumor after prior vaccination.