Basic research for antitumor immune response induced by dendritic cells pulsed with lysate of HSV-1-infected tumor cells

HSV-1感染肿瘤细胞裂解物脉冲树突状细胞诱导抗肿瘤免疫反应的基础研究

• 批准号: 17591501
• 负责人: TANAKA Minoru
• 金额: $ 1.98万
• 依托单位: The 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: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17591501/
• 关键词: dendritic cell; HSV-1; Neuro 2a; A; J mouse; antitumor immune response; MHC class I; MHC class II; Oncolytic virus; dendritic cell; HSV-1; Neuro 2a; J mouse; antitumor immune response; MHC class I; MHC class II; Oncolytic virus; ウイルス; 免疫

In this study, we used oncolytic herpes simplex viruses as a new treatment for malignant brain tumors, researching methods to activate a tumor antigen more effectively than only using dendritic cells pulsed with a tumor antigen in tumor lysate.For anti-tumor effect, it is important to get co-stimulation acceptor stimulation as well as presenting tumor antigens to MHC I molecule. In order for T-lymphocytes to recognize the tumor antigen, MHC class II protein must also accompany the processed tumor antigen. We made subcutaneous tumor model of Neuro 2a and N18, neuroblastoma cell line of A/J mice. We used bone marrow-derived dendritic cells from A/J mice in order to confirm induction of antitumor immune response. As a result, antitumor immune response did not induced by pulsing these denciritic cells with lysate of T-01(HSV-1)-infected Neuro 2a tumor cells. However, we succeeded in induction of antitumor immune response by dendritic cells pulsed with N18 tumor cells.

In this study, we used oncolytic herpes simplex viruses as a new treatment for malignant brain tumors, researching methods to activate a tumor antigen more effectively than only using dendritic cells pulsed with a tumor antigen in tumor lysate.For anti-tumor effect, it is important to get co-stimulation acceptor stimulation as well as presenting tumor antigens to MHC I molecule.为了使T淋巴细胞识别肿瘤抗原，MHC II类蛋白也必须伴随加工后的肿瘤抗原。我们制造了神经2a和N18的皮下肿瘤模型，即A/J小鼠的神经母细胞瘤细胞系。我们使用了来自A/J小鼠的骨髓衍生的树突状细胞，以确认诱导抗肿瘤免疫反应。结果，没有通过用T-01（HSV-1）感染的神经2A肿瘤细胞裂解这些denciritic细胞来诱导抗肿瘤免疫反应。但是，我们成功地通过N18肿瘤细胞脉冲的树突状细胞成功诱导了抗肿瘤免疫反应。

项目成果

Oncolytic virus therapy for glioma.

胶质瘤的溶瘤病毒治疗。

• 发表时间: 2005
• 期刊: Glioma-Clinical Pathology and Therapy (Tabuchi K (ed.)), Tokyo, Springer-Verlag
• 作者: Todo T;Ino Y
• 通讯作者: Ino Y

Functional neuronavigation co-utilizing tractography and white matter mapping (in Japanese)

联合使用纤维束成像和白质绘图的功能神经导航（日语）

• 发表时间: 2005
• 期刊: Currently Practical Neurosurgery 15(8)
• 作者: Kamada K;Todo T;Kawahara N;Kawai K;Morita A;Kirino T
• 通讯作者: Kirino T

Oncolytic virus therapy using genetically engineered herpes simplex viruses

• DOI: 10.1111/j.1749-0774.2002.tb00109.x
• 发表时间: 2002-08
• 期刊: Human Cell
• 影响因子: 4.3
• 作者: T. Todo

Development of oncolytic replication-competent herpes simplex virus vectors : the G207 paradigm.

具有溶瘤复制能力的单纯疱疹病毒载体的开发：G207范例。

• 发表时间: 2004
• 期刊: Cancer Gene Therapy (Curiel DT, Douglas JT (eds)), Totowa, NJ, Humana Press
• 作者: Todo T;Rabkin SD
• 通讯作者: Rabkin SD

Brain tumor therapy using oncolytic herpes simplex virus type I. (in Japanese)

使用 I 型溶瘤单纯疱疹病毒治疗脑肿瘤。（日语）

• 发表时间: 2005
• 期刊: BIO Clinica 20(12)
• 作者: Miyamoto S;Todo T
• 通讯作者: Todo T