Effective induction of antiglioma cytotoxic T cells by coadministration of heat-induction antigen by means of bio-nanoparticles dendritic cells

通过生物纳米粒子树突状细胞共同施用热诱导抗原有效诱导抗神经胶质瘤细胞毒性T细胞

• 批准号: 16390409
• 负责人: WAKABAYASHI Toshihiko
• 金额: $ 9.28万
• 依托单位: Nagoya University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 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/grant/KAKENHI-PROJECT-16390409/
• 关键词: Dendritic cell; Cell Therapy; Heat-induction antigen; Glioma; Immunity; CTL; マグネタイト; ナノ粒子; 温熱療法; 脳腫瘍; リポソーム; 免疫誘導; ヒートショックタンパク; 誘導磁場

As it is well known that heat-induction particles enhance the stimulatory activity of dendritic cells (DCs), we hypothesized that DCs in the presence of the heat-induction antigens would provide particularly effective antitumor activity against glioma cells by stimulating cytotoxic T cell. As a fundamental study, a rat glioma cell line T-98 was heated with bio-nano particles, magnetite, under the alternative magnetic field to continue the adequate concentration level of heat-induction antigens around the tumor cells, then cocultured with syngeneic bone marrow-derived DCs and naive splenic T cells. The T-98 cells were almost completely killed cocluture with DCs and T cells, and strong tumor-specific cytotoxic T lymphocyte (CTL) activity was induced. As a pre-clinical study, human DCs accumulated from peripheral blood CD14 positive monocyte was activated with IL-2 and GM-CSF and analyzed the expression of cytokine level in culture. Remarkable elevation of expression level of interleukin-12 and IFN-gamma could be observed in culture which may activate T lymphocytes. These result suggest that heat-induction antigen would stimulate DCs and induce antitumor immunity against glioma by coculturing with T lymphocytes which may act as displaying lytic activity against glioma.

众所周知，热诱导颗粒可增强树突状细胞 (DC) 的刺激活性，因此我们假设，在热诱导抗原存在下，DC 将通过刺激细胞毒性 T 细胞，对神经胶质瘤细胞提供特别有效的抗肿瘤活性。作为一项基础研究，大鼠神经胶质瘤细胞系 T-98 在交变磁场下用生物纳米颗粒、磁铁矿加热，以持续使肿瘤细胞周围的热诱导抗原达到足够的浓度水平，然后与同源骨髓来源的 DC 和初始脾 T 细胞共培养。 T-98细胞与DC和T细胞共混几乎被完全杀死，并诱导出强烈的肿瘤特异性细胞毒性T淋巴细胞(CTL)活性。作为一项临床前研究，用IL-2和GM-CSF激活从外周血CD14阳性单核细胞积累的人DC，并分析培养物中细胞因子水平的表达。在培养物中可以观察到白介素12和IFN-γ的表达水平显着升高，这可能激活T淋巴细胞。这些结果表明，热诱导抗原可以通过与T淋巴细胞共培养来刺激DC并诱导针对神经胶质瘤的抗肿瘤免疫，而T淋巴细胞可能表现出针对神经胶质瘤的裂解活性。

项目成果

Aurora-B dysfunction of multinucleated giant cells in glioma detected by site-specific phosphorylated antibodies

• DOI: 10.3171/jns.2004.101.6.1012
• 发表时间: 2004-12-01
• 期刊: JOURNAL OF NEUROSURGERY
• 影响因子: 4.1
• 作者: Fujita, M;Mizuno, M;Yoshida, J
• 通讯作者: Yoshida, J

Multicentric Atypical teratoid/Rhabdoid tumors occurring in the eye and fourth ventricle of an infant.

多中心非典型畸胎瘤样/横纹肌样肿瘤发生在婴儿的眼睛和第四脑室。

• 发表时间: 2005
• 期刊: J Neurosurg 102(3)
• 作者: Fujita M;et al.
• 通讯作者: et al.

バイオナノテクノロジーを用いた温熱療法(先端医療シリーズ29・脳神経外科の最新医療)

利用生物纳米技术的热疗（高级医疗系列29/神经外科最新医疗）

• 发表时间: 2004
• 作者: 若林俊彦;他
• 通讯作者: 他

Interferon-beta gene therapy for cancer : basic research to clinical application.

癌症干扰素-β基因治疗：基础研究到临床应用。

• 发表时间: 2004
• 期刊: Cancer Sci 95(11)
• 作者: Yoshida J;et al.
• 通讯作者: et al.

Human gene therapy for malignant gliomas (glioblastoma multiforme and anaplastic astrocytoma) by in vivo transduction with human interferon beta gene using cationic liposomes.

• DOI: 10.1089/10430340460732472
• 发表时间: 2004-07
• 期刊: Human gene therapy
• 影响因子: 4.2
• 作者: J. Yoshida;M. Mizuno;M. Fujii;Y. Kajita;Norimoto Nakahara;M. Hatano;R. Saito;Misato Nobayashi;T. Wakabayashi