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目的 :探讨来源于HER2 /neu原癌蛋白的多肽诱导特异性细胞免疫应答及其在体内的抗癌效应。方法 :利用合成的2个具有小鼠H 2Kd 分子结合基序的HER2 /neu肽作为肿瘤排斥抗原 ,在体外刺激小鼠脾淋巴细胞以及皮下免疫小鼠 ,观察淋巴细胞的增殖能力、CTL的杀伤活性以及HER2 /neu肽的抑瘤作用。结果 :HER2 /neu肽在体内和体外对BALB/c小鼠淋巴细胞的增殖都有明显的促进作用。HER2 /neu肽免疫BALB/c小鼠后 ,可以从小鼠淋巴细胞中诱导出肽特异性CTL ,这些CTL可以特异地杀伤HER2 /neu阳性SP2 / 0细胞 ,而对HER2 /neu阴性SP2 / 0细胞却无明显的杀伤活性。SP2 / 0HER2细胞在HER2 /neu肽免疫小鼠体内的生长受到抑制。结论 :研究结果表明HER2 /neu肽可以起到一定的抑瘤保护作用 ,提示 ,肿瘤特异性抗原来源的MHC Ⅰ类分子肽表位作为疫苗进行肿瘤免疫治疗是可行的。
Objective: To investigate the specific cellular immune response induced by HER2/neu proto-oncogene protein and its anticancer effect in vivo. METHODS: Two synthesizing HER2/neu peptides with mouse H2Kd molecule binding motifs were used as tumor rejection antigens to stimulate spleen lymphocytes in mice and immunize mice in vitro. The proliferation of lymphocytes and CTL killing were observed. Activity and inhibitory effect of HER2/neu peptide. RESULTS : HER2 /neu peptide significantly promoted the proliferation of lymphocytes in BALB/c mice in vivo and in vitro. After immunizing BALB/c mice with HER2/neu peptides, peptide-specific CTLs can be induced from mouse lymphocytes. These CTLs can specifically kill HER2/neu-positive SP2 / 0 cells, while the HER2 / neu-negative SP2 / 0 cells. There is no obvious killing activity. The growth of SP2 / 0HER2 cells in HER2-neu peptide-immunized mice was inhibited. Conclusion: The results of the study show that HER2 /neu peptide can play a role in the protection of tumors, suggesting that tumor-specific antigen-derived MHC class I peptide epitopes as vaccines for tumor immunotherapy are feasible.