Combination immunotherapy with radiation and CpG-based tumor vaccination for the eradication of radio- and immuno-resistant lung carcinoma cells
Combination immunotherapy with radiation and CpG-based tumor vaccination for the eradication of radio- and immuno-resistant lung carcinoma cells
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DOI：
10.1111/j.1349-7006.2009.01114.x
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发表时间：
2009-05-01
期刊：
影响因子：
5.7
通讯作者：
Nishimura, Takashi
中科院分区：
文献类型：
--
作者：
Chamoto, Kenji;Takeshima, Tsuguhide;Nishimura, Takashi
含有未甲基化胞嘧啶-硫代磷酸-鸟嘌呤的寡脱氧核苷酸 (CpG-ODN) 被认为是 Toll 样受体 9 (TLR9) 的配体，可选择性激活 1 型免疫。我们已经报道，用与模型肿瘤抗原卵清蛋白（OVA）（CpG + OVA-脂质体）共封装的脂质体-CpG对荷瘤小鼠进行疫苗接种，可以使荷有表达OVA的EG-7淋巴瘤细胞的小鼠完全治愈。然而，相同的疗法不能有效根除Lewis肺癌（LLC）-OVA-癌。为了克服 LLC-OVA 的难治性，我们尝试了放射治疗与基于 CpG 的肿瘤疫苗接种的联合治疗。当皮内（i.d.）注射到 C57BL/6 中的 LLC-OVA-癌变得明显（7-8 mm）时，以 14 Gy 的剂量以 24 小时的间隔对小鼠进行两次照射。第二次放射后，CpG + OVA-脂质体经腹腔注射。在肿瘤块的引流淋巴结（DLN）附近施用。放射加CpG+OVA-脂质体治疗的小鼠肿瘤生长受到极大抑制，约60%的治疗小鼠完全治愈。此外，放射线和CpG + OVA-脂质体的联合治疗可以在荷瘤小鼠的DLN中增强OVA-四聚体(+) LLC-OVA特异性细胞毒性T淋巴细胞(CTL)的诱导。这些结果表明，放射治疗与基于 CpG 的肿瘤疫苗的联合治疗是根除顽固性癌症的有效策略。 （《癌症科学》2009 年；100：934-939）。
Unmethylated cytosine-phosphorothioate-guanine containing oligodeoxynucleotides (CpG-ODN) is known as a ligand of toll-like receptor 9 (TLR9), which selectively activates type-1 immunity. We have already reported that the vaccination of tumor-bearing mice with liposome-CpG coencapsulated with model-tumor antigen, ovalbumin (OVA) (CpG + OVA-liposome) caused complete cure of the mice bearing OVA-expressing EG-7 lymphoma cells. However, the same therapy was not effective to eradicate Lewis lung carcinoma (LLC)-OVA-carcinoma. To overcome the refractoriness of LLC-OVA, we tried the combination therapy of radiation with CpG-based tumor vaccination. When LLC-OVA-carcinoma intradermally (i.d.) injected into C57BL/6 became palpable (7-8 mm), the mice were irradiated twice with a dose of 14 Gy at intervals of 24 h. After the second radiation, CpG + OVA-liposome was i.d. administered near the draining lymph node (DLN) of the tumor mass. The tumor growth of mice treated with radiation plus CpG + OVA-liposome was greatly inhibited and approximately 60% of mice treated were completely cured. Moreover, the combined therapy with radiation and CpG + OVA-liposome allowed the augmented induction of OVA-tetramer(+) LLC-OVA-specific cytotoxic T lymphocyte (CTL) in DLN of tumor-bearing mice. These results indicate that the combined therapy of radiation with CpG-based tumor vaccine is a useful strategy to eradicate intractable carcinoma. (Cancer Sci 2009; 100: 934-939).