RESEARCH IN IMMUNOLOGICAL DIAGNOSIS AND VACCINATION THERAPY AGAINST BRAIN TUMORS USING ANTI-IDIOTYPIC ANTIBODY.

使用抗独特型抗体进行脑肿瘤免疫诊断和疫苗接种治疗的研究。

• 批准号: 02807133
• 负责人: KOKUNAI Takashi
• 金额: $ 1.09万
• 依托单位: KOBE UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1990
• 资助国家: 日本
• 起止时间: 1990 至 1992
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-02807133/
• 关键词: monoclonal antibody; anti-idiotypic antibody; brain tumor; idiotypic network; vaccination therapy; モノクロ-ナル抗体; イディオタイプネットワ-ク; 免療療法

1), Rat anti-idiotypic antibody (Ab_2) was prepared by the immunization of monoclonal antibody (RS-11, Ab_1) recognized of the common antigen in species of human, rat and mouse. The anti-anti-idiotypic antibody (Ab_3) and the increased activity of killer cell in spleen were induced by the immunization of Ab_2. When the rat glioma cells were transplanted following the immunization of Ab_2, tumor growth was inhibited compared to controls. This tumor growth inhibiting effect was exaggerated by the inhibition of the activity of suppressor T lymphocytes.2), Anti-idiotypic antibody (Idio-33) was prepared using the human monoclonal antibody (CLN-IgG) recognized of the human brain tumor associated antigen (TA226). Idio-33 was beta type of anti-idiotypic antibody. In the scid mice with the reconstruction of human immune system, the inhibitory effect of tumor growth of human gliomas were found by the treatment with the immunization of Idio-33. And Ab_3 was induced in the sera of scid mice. The peripheral lymphocytes in the patients treated with CLN-IgG produced the Ab_3 by the stimulation with Idio-33. Anti-idiotope was expressed in the cell surface of B lymphocytes and also helper T lymphocytes.

1)、大鼠抗独特型抗体(Ab2)是用识别人、大鼠和小鼠共同抗原的单抗(RS-11、Ab1)免疫制备的。抗独特型抗体(Ab3)免疫后，小鼠脾内杀伤细胞活性增强。免疫后移植大鼠胶质瘤细胞，肿瘤生长受到抑制。这种抑制肿瘤生长的作用因抑制T淋巴细胞的活性而被夸大。2)用人脑肿瘤相关抗原(TA226)识别的人单抗(CLN-Ig G)制备抗独特型抗体(Idio-33)。IDIO-33为Beta型抗独特型抗体。在重建了人类免疫系统的SCID小鼠中，发现Idio-33免疫治疗对人脑胶质瘤的生长有抑制作用。并在SCID小鼠血清中诱导产生抗体3。CLN-Ig G治疗后患者的外周血淋巴细胞在Idio-33刺激下产生抗体3。抗独特体表达于B淋巴细胞和辅助性T淋巴细胞的细胞表面。

项目成果

H.Kudo: "Quantitative analysis of glutathione in human brain tumors." G.Neurosurgery. 72. 610-615 (1990)

H.Kudo：“人脑肿瘤中谷胱甘肽的定量分析。”

T.Kokunai: "Analysis of anti-idiotypic antibody related to brain tumor associated antigen (TA226)." Neuroimmunological Res.5. (1993)

T.Kokunai：“与脑肿瘤相关抗原（TA226）相关的抗独特型抗体的分析。”

T.Kokunai: Kimpodo. Immunology and molecular biology. 3, Treatment with monoclonal antibody., 344 (1992)

T.Kokunai：金波多。

T.Kokunai: "Antigen related to cell proliferation in malignant gliomas recognized by a human monoclonal antibody." Jouranal of Neurosurgery. 73. 901-908 (1990)

T.Kokunai：“人类单克隆抗体识别出与恶性神经胶质瘤细胞增殖相关的抗原。”

T.Kokunai: "Differentiation of a medulloblastoma cell line mediated by protein kinase A." Biological Aspects pf Brain Tumors. 436-441 (1991)

T.Kokunai：“蛋白激酶 A 介导的髓母细胞瘤细胞系的分化。”