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Human monoclonal antibody against human, malignant glioma obtained from mouse-human hetero hybridoma system

从小鼠-人异种杂交瘤系统获得的抗人恶性神经胶质瘤的人单克隆抗体

基本信息

批准号：
60570660
负责人：
NAKAGAWA Kunio
金额：
$ 0.77万
依托单位：
The University of Tsukuba
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1985
资助国家：
日本
起止时间：
1985 至 1986
项目状态：
已结题

项目摘要

Tumor specific treatment or diagnostic modalities against malignant brain-tumor are necessary to decrease the surrounding normal tissue damage. In this meaning, monoclonal antibody should be useful. Up to date, most of the monoclonal antibodies have been made of mouse-mouse hybridoma system. For the purpose of clinical use, human immunoglobulin against human malignant tumor is necessary. In this investigation, several human immunoglobulin G (IgG) were obtained from hybridoma cell lines between mouse myeloma cells (P3Ul) and human peripheral blood lymphocytes. Ten of these human IgGs, showed well response with 5 different human glioma but did not respond with 2 human medulloblastomas and one metastatic brain tumor at all under PAP immunohistochemical analysis. However, peroxydase-labeled anti-human IgG, used as the second antibody, crossed with human glioma cells.To avoid this cross-reactivity, anti-human IgG was added before the use of antihuman-glioma IgG and peroxydase-labeled anti-human IgG. This pretreatment well blocked the cross-reactivity between glioma cells and B-cells. In conclusion, ten anti-human-glioma IgG were obtained from mouse-human heterohybridoma system. There are several problems to be solved, including removal of fetal calf serum containing in the culture medium, further purification and more investigation about specificity using much more tumor panel and/or normal tissues.

针对恶性脑肿瘤的特异性治疗或诊断模式是必要的，以减少周围正常组织的损害。在这个意义上，单克隆抗体应该是有用的。迄今为止，大多数单克隆抗体都是通过鼠-鼠杂交瘤系统制备的。为了临床应用，抗人类恶性肿瘤的人免疫球蛋白是必需的。本研究从小鼠骨髓瘤细胞（P3 U1）与人外周血淋巴细胞杂交瘤细胞系中获得了几种人IgG。在PAP免疫组织化学分析中，这些人IgG中的10个对5种不同的人胶质瘤显示出良好的反应，但对2种人髓母细胞瘤和1种转移性脑肿瘤没有反应。但过氧化物酶标记的抗人IgG作为第二抗体与人脑胶质瘤细胞发生交叉反应，为了避免这种交叉反应，在使用抗人脑胶质瘤IgG和过氧化物酶标记的抗人IgG之前加入抗人IgG。这种预处理很好地阻断了胶质瘤细胞和B细胞之间的交叉反应。结果表明，从鼠-人杂交瘤系统中获得了10株抗人胶质瘤IgG。目前尚存在一些问题需要解决，包括培养基中胎牛血清的去除、进一步纯化以及更多肿瘤和/或正常组织的特异性研究。