Basic research of peptide vaccine as therapeutic cancer vaccine

我们从人类肿瘤相关抗原中鉴定出相对大量的多肽抗原，这些抗原可被人类白细胞抗原IA类限制性细胞毒性T淋巴细胞识别。这些多肽抗原可与不同类型的人类白细胞抗原A类分子结合，包括人类白细胞抗原A2(0201、0206和0207)、A3、A1101、A2402、A26、A3101和A3303。在绝大多数日本人(&gt；98%)和亚洲人(&gt；90%)和其他种族(&gt；70%)中，至少有一种这种人类白细胞抗原分子表达。因此，这些已鉴定的多肽可能适用于以多肽为基础的癌症免疫治疗。我们还发现，在癌症患者的血浆中可以检测到这些多肽的特异性免疫球蛋白G，这表明这些多肽具有与T辅助细胞的反应性。这些结果使我们能够在接种前测量对多肽具有高反应性的多肽特异性免疫球蛋白，并只给癌症患者注射反应性多肽(个性化多肽疫苗)。事实上，我们最近报道，通过随机临床试验，这些个性化的多肽疫苗为癌症患者提供了最喜欢的临床反应。总之，我们可以为多肽疫苗作为治疗性肿瘤疫苗提供科学依据。

We identified relatively large numbers of peptide antigens from human tumor associated antigens that were recognized by HLA-class IA-restricted cytotixic T lymphocytes. These peptide antigens could bind to different types of HLA-class IA molecules, including HLA-A2 (0201, 0206, and 0207), A3, A1101, A2402, A26, A3101, and A3303. At least one of these HLA molecules were expressed in the vast majority of Japanease (>98%) and Asians (>90%), and the other ethnics (>70%). Therefore, these identified peptides could be applicable for peptide-based cancer immunotherapy to cancer in the world. We also found that IgG specific to these peptides were detectable in plasma of cancer patients, suggesting the reactivity of these peptides to T helper cells. These results allowed us a pre-vaccination measurement of peptide-specific IgG highly reactive to peptides, and administration of only reactive peptides to cancer patients (personalized peptide vaccination). Indeed, we recently reported these personalized peptide vaccination provided favorite clinical responses to cancer patients through a randomized clinical trial. Collectively, we could provide scientific basis of peptide vaccine as therapeutic cancer vaccine.