Basic research of cancer immunotherapy by using dendritic cells and clinical applications for head and neck tumors ; by using galactosylceramide

树突状细胞肿瘤免疫治疗的基础研究及头颈部肿瘤的临床应用；

• 批准号: 16591980
• 负责人: HASHIMOTO Wataru
• 金额: $ 2.3万
• 依托单位: TOHOKU UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16591980/
• 关键词: galactosylceramide; antitumor effect; natural killer T cells; IFN-γ; apoptosis; dendritic cells; innate immunity; head and neck tumor; 頭頸部腫瘍

Dendritic cells (DCs) are specialized APCs which have an effective antitumor immuno response. DCs are expected to using cancer immunotherapy. A glycolipid antigen, α-Galactosylceramide(α-GalCer) is presented by a class Ib molecule, CD1d, and stimulates V α14 NKT cells, resulting in a rapid induction of IL-4 and IFN-γ.We have investigated the antitumor effects of α-GalCer clarified that intratumoral onjection with α-GalCer treated-DCs resulted in regression of day 7 established poorly immunogenic tumors. We also clarified that these antitumor effects of α-GalCer treated-DCs were almost reduced in V α14NKT-deficient mice, suggesting that V α14 NKT cells are sufficient for these antitumor effects.In this project, we investigated the antitumor effects of α-GalCer in human model in detail. Phenotypic analysis revealed an expansion of CD56+ CD161+ CD3+Vα24 TCR NKTcells on PBMC. These results suggest that NKT cells are also effector cells for α-GalCer -induced tumor apoptosis on human model.Next, we analyzed a response to α-GalCer on PBMC from oral cancer patient. We collected patients' PBMC before and after chemotherapy, and investigated changes of NK or NKT cells. In this study, we have applied to committee of Tohoku University Hospital for the clinical application and were permitted. Then, we have started to collect clinical samples and got some samples. But we cannot analyze data because sample numbers were not so much. We hope that we will continue collecting samples from cancer patients and develop cancer immunotherapy by using α-GalCer treated-DCs.

树突状细胞（Dendritic cells，DCs）是一种具有抗肿瘤免疫应答的特化APC。DC有望用于肿瘤免疫治疗。糖脂抗原α-半乳糖神经酰胺（α-GalCer）由Ib类分子CD 1d呈递，并刺激V α14 NKT细胞，导致IL-4和IFN-γ的快速诱导。我们研究了α-GalCer的抗肿瘤作用，阐明了肿瘤内注射α-GalCer处理的DC导致第7天建立的免疫原性差的肿瘤消退。我们还阐明了α-GalCer处理的DC在V α 14 NKT缺陷小鼠中的这些抗肿瘤作用几乎被降低，这表明V α14 NKT细胞足以发挥这些抗肿瘤作用。表型分析显示PBMC上CD 56 + CD 161 + CD 3 +Vα24 TCR NKT细胞扩增。这些结果表明，NKT细胞也是α-GalCer诱导的肿瘤凋亡的效应细胞。接下来，我们分析了口腔癌患者PBMC对α-GalCer的反应。分别于化疗前后采集患者外周血单个核细胞（PBMC），观察NK细胞和NKT细胞的变化。在本研究中，我们向东北大学医院委员会申请了临床应用，并获得了许可。然后，我们已经开始收集临床样本，并获得了一些样本。但是我们不能分析数据，因为样本数量不是那么多。我们希望我们将继续收集癌症患者的样本，并通过使用α-GalCer处理的DC开发癌症免疫治疗。