Essential roles of tumor-derived helper T cell epitopes for an effective peptide-based tumor vaccine.
Essential roles of tumor-derived helper T cell epitopes for an effective peptide-based tumor vaccine.
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发表时间：
2003
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通讯作者：
Lijie Wang;Y. Miyahara;Takuma Kato;Linan N. Wang;T. Aota;K. Kuribayashi;H. Shiku
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作者：
Lijie Wang;Y. Miyahara;Takuma Kato;Linan N. Wang;T. Aota;K. Kuribayashi;H. Shiku
在这项研究中，我们鉴定了一个c-erbB-2/HER2/neu （HER2）衍生的Th表位（HER2(16-30)），并研究了Th表位在HER2特异性CD8+ T细胞诱导和体内肿瘤根除中的作用，特别强调了肿瘤细胞衍生的Th表位的作用。用HER2表位（16-30）和CTL表位HER2（63-71）的混合物皮下注射小鼠GM-CSF （mGM-CSF）免疫BALB/c小鼠，诱导的HER2（63-71）特异性CD8+ T细胞水平比单独使用CTL表位获得的高得多。与HER2无关的OVA衍生的Th表位（OVA(323-339)）在HER2（63-71）特异性CD8+ T细胞诱导中表现出类似的增强作用。然而，只有用HER2（16-30）和HER2（63-71）免疫的小鼠，而不是用与肿瘤无关的卵细胞（323-339）和HER2（63-71）免疫的小鼠，在体内显示了表达HER2而不表达卵细胞的CMS5mHE肿瘤细胞的根除。这种区别是在预防和治疗实验设置观察到的。相反，HER2（16-30）和OVA (323-339) Th表位在诱导根除既表达HER2又表达OVA的CMS5mHEOVA肿瘤细胞方面同样有效。我们的研究结果清楚地表明，靶向肿瘤细胞来源的CTL和Th表位可以有效地诱导体内抗肿瘤免疫。
In this study, we identified a c-erbB-2/HER2/neu (HER2)-derived Th epitope (HER2 (16-30) ) and examined the role of Th epitopes in HER2-specific CD8+ T cell induction and in vivo tumor eradication, with a particular emphasis on the role of tumor cell-derived Th epitopes. Immunization of BALB/c mice using a mixture of Th epitope HER2 (16-30) and CTL epitope HER2 (63-71) administered subcutaneously with murine GM-CSF (mGM-CSF) induced a much higher level of HER2 (63-71) -specific CD8+ T cells compared with that obtained with the CTL epitope alone. HER2-unrelated OVA-derived Th epitope (OVA (323-339) ) exhibited a similar enhancing effect on HER2 (63-71) -specific CD8+ T cell induction. However, only mice immunized with HER2 (16-30) and HER2 (63-71), but not with a tumor-unrelated OVA (323-339) and HER2 (63-71), showed in vivo eradication of CMS5mHE tumor cells expressing HER2 but not OVA. This distinction was observed in preventative as well as therapeutic experimental settings. Conversely, both HER2 (16-30) and OVA (323-339) Th epitopes were equally effective in inducing the eradication of CMS5mHEOVA tumor cells which express HER2 as well as OVA. Our results clearly indicate that CTL and Th epitopes of target tumor cell origin should be used for effective induction of in vivo antitumor immunity.