Successful tumor eradication was achieved by collaboration of augmented cytotoxic activity and anti-angiogenic effects following therapeutic vaccines containing helper-activating analog-loaded dendritic cells and tumor antigen DNA
Successful tumor eradication was achieved by collaboration of augmented cytotoxic activity and anti-angiogenic effects following therapeutic vaccines containing helper-activating analog-loaded dendritic cells and tumor antigen DNA
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DOI：
10.1007/s00262-006-0192-0
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发表时间：
2006-08
期刊：
影响因子：
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通讯作者：
K. Teramoto;K. Kontani;T. Fujita;Y. Ozaki;S. Sawai;N. Tezuka;S. Fujino;Y. Itoh;O. Taguchi;R. Kannagi;K. Ogasawara
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文献类型：
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作者：
K. Teramoto;K. Kontani;T. Fujita;Y. Ozaki;S. Sawai;N. Tezuka;S. Fujino;Y. Itoh;O. Taguchi;R. Kannagi;K. Ogasawara
我们以前报道，鸽子细胞色素C衍生肽（泛IA），有效地结合广泛的MHC II类分子，激活小鼠辅助性T细胞（Th）功能。在实验模型中，Pan-IA DNA疫苗增强了肿瘤抗原免疫小鼠的抗肿瘤免疫力。为了在治疗环境中引发更有效的抗肿瘤免疫并根除肿瘤，将Pan-IA负载的树突状细胞（DC）与包括卵清蛋白（OVA）抗原DNA的疫苗组合接种于荷瘤小鼠中。70%的免疫小鼠在治疗后无肿瘤存活至少4个月。相比之下，接种OVA DNA的小鼠（无论是否有幼稚DC）都没有消除肿瘤并在5周内死亡。仅在用OVA DNA和Pan-IA负载的DC接种的小鼠中，在脾和肿瘤部位以及在接种部位诱导了特异于OVA的细胞毒性和辅助应答。此外，在这些小鼠的肿瘤中观察到OVA特异性CD 4+和CD 8 +T淋巴细胞的积累和干扰素-γ介导的抗血管生成。因此，联合疫苗接种引发肿瘤特异性细胞毒性和辅助免疫，导致增强的肿瘤裂解能力和抗血管生成作用。这是第一份报告表明，大多数已建立的肿瘤被成功根除的合作，有效的抗肿瘤免疫和抗血管生成的效果，通过接种肿瘤抗原和辅助激活类似物。这种新的疫苗接种策略是广泛适用的，无论在目标分子中识别辅助表位，并有助于治疗性癌症疫苗的开发。
We reported previously that pigeon cytochrome c-derived peptides (Pan-IA), which bind broad ranges of MHC class II molecules efficiently, activate T helper (Th) function in mice. In an experimental model, Pan-IA DNA vaccines augmented antitumor immunity in tumor antigen-immunized mice. To elicit more potent antitumor immunity and to eradicate tumors in a therapeutic setting, Pan-IA-loaded dendritic cells (DCs) were inoculated in combination with vaccines including ovalbumin (OVA) antigen DNA in tumor-bearing mice. Seventy percent of the immunized mice survived tumor-free for at least 4 months after treatment. In contrast, mice vaccinated with OVA DNA, either with or without naïve DCs, did not eliminate the tumors and died within 5 weeks. Only in mice vaccinated with OVA DNA and Pan-IA-loaded DCs were both cytotoxic and helper responses specific for OVA induced at the spleen and tumor sites as well as at the vaccination sites. Furthermore, accumulation of OVA-specific CD4+and CD8+T lymphocytes and interferon-gamma-mediated anti-angiogenesis were observed in the tumors of these mice. Thus, the combined vaccination primed both tumor-specific cytotoxicity and helper immunity resulting in augmented tumor lysis ability and anti-angiogenic effects. This is the first report to show that most established tumors were successfully eradicated by collaboration of potent antitumor immunity and anti-angiogenic effects by vaccination with tumor antigens and helper-activating analogs. This novel vaccination strategy is broadly applicable, regardless of identifying helper epitopes in target molecules, and contributes to the development of therapeutic cancer vaccines.