Establishment of New Immunotheapy using Dendritic Cells and Evaluation of Its Inhibitory Effect on Tumor Relapse.

树突状细胞新型免疫疗法的建立及其对肿瘤复发的抑制作用评价。

• 批准号: 09671283
• 负责人: OSADA Takuya
• 金额: $ 1.92万
• 依托单位: University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09671283/
• 关键词: Immunotherapy; Dendritic Cell; Tumor Antigen; Gastrointestinal Cancer; Cytokine

Dendritic cell (DC) is known to be a potent antigen presenting cell which can elicit primary immunoreaction. New immunotherapy using DCs are recently applied to malignant lymphoma and malignant melanoma, showing hopeful results. In this study, we tried to use this new immunological method to other malignancies, with special regard to gastrointestinal cancers. From our results, the optimal method of DC separation and tumor antigen purification was determined. Using murine tumor metastasis model, we evaluated the in vivo antitumor effect of this therapy.Comparing three groups, intraperitoneal injection of recombinant murine GM-CSF, pretreatment with GM-CSF gene transduced hepatocytes (intrasplenic injection), and control group, we found that the local supply of GM-CSF is important for eliciting strong antitumor immunity in the liver. We hope our findings would be helpful for the establishment of human antitumor immunotherapy that can inhibit tumor relapse after surgery.

树突状细胞（DC）是一种有效的抗原提呈细胞，可引起原发性免疫反应。近年来，利用树突状细胞的新型免疫疗法被应用于恶性淋巴瘤和恶性黑色素瘤的治疗，取得了可喜的成果。在本研究中，我们尝试将这种新的免疫学方法用于其他恶性肿瘤，特别是胃肠道肿瘤。根据我们的结果，确定了DC分离和肿瘤抗原纯化的最佳方法。通过小鼠肿瘤转移模型的体内抗肿瘤作用的研究，比较了重组小鼠GM-CSF腹腔注射组、转GM-CSF基因肝细胞预处理组（脾内注射）和对照组，发现GM-CSF的局部供应对于激发肝脏的抗肿瘤免疫是重要的。我们希望我们的研究结果将有助于建立人类抗肿瘤免疫治疗，可以抑制肿瘤术后复发。

项目成果

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Takamizawa M、Rivas A：“处理并向幼稚 T 淋巴细胞呈递标称抗原的树突状细胞源自 CD2 前体。”

Osada T,Sakamoto M et al.: "Acguisinon of glutamine synthetase exprossion in human hepatocacimegenesis" Cancer. 85. 819-831 (1999)

Osada T、Sakamoto M 等人：“人类肝细胞生成中谷氨酰胺合成酶表达的Acguisinon”癌症。

Maejima M,Shibata Y. et al.: "Immunotherapy bofore and furing pregrancy improves pregnancy outcime in women who suffer from recurrent abortion and did rst lenef.T from immunotherapy befeva pregnany." Am.J.Reprod.Immunol.39. 12-15 (1998)

Maejima M、Shibata Y. 等人：“怀孕前和怀孕前的免疫治疗可改善患有反复流产并在怀孕前首次接受免疫治疗的女性的妊娠结局。”

Osada T,Sakamoto M,et al: "Increased Ubiguitin immunoroactivity in hepatocellular carcinoma and precaucerous lesions in the liver" Journal of Hepatology. 26. 1266-1273 (1997)

Osada T、Sakamoto M 等人：“肝细胞癌和肝脏癌前病变中泛素免疫活性增加”《肝脏病学杂志》。