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Biochemical studies and medical application of immunoregulatory factors

免疫调节因子的生化研究及医学应用

基本信息

批准号：
60440093
负责人：
OSAWA Toshiaki
金额：
$ 16.32万
依托单位：
The University of Tokyo
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (A)
财政年份：
1985
资助国家：
日本
起止时间：
1985 至 1987
项目状态：
已结题

项目摘要

1. Lymphokines produced by human T cell hybridomas : We established a novel selection method for the construction of human T cell hybridomas using metabolic inhibitors (emetine and actinomycin D). From one of human T cell hybridoma clones thus established, we cloned cDNA for human lymphotoxin and succeeded to produce a large amounts of recombinant human lymphotoxin. The recombinant human lymphotoxin was found to exert potent cytotoxicity specifically against malignant cells in vitro and in vivo. On the process of the analysis of in vivo anti-tumor activity of human lymphotoxin, we found that human lymphotoxin has potent macrophage chemotactic and macrophage activating activities. From the other human T cell hybridoma clone, H3-E9-6, we partially purified two macrophage activating factors. One of them, MAF-CI, is a priming factor which is not identical with human <gamma>-interferone. The other, MAF-CII, is a triggering factor which is different from lipopolysaccharide. These two macrophage activating factors show a synergistic effect on human monocytes and induce strong tumoricidal activity of human monocytes. Now we are wroking on the complete purification and structural study of these two factors.2. Monokines produced by human and mouse macrophage hybridomas : We succeeded to establish a number of mouse and human macrophage hybridomas and analyzed various monokines produced by these macrophage hybridomas. One of the human macrophage hybridoma clones established was found to secrete a potent tumor-specific cytotoxin which was distinct from human lymphotoxin, tumor necrosis factor and interleukin-1.

1.人T细胞杂交瘤产生的趋化因子：我们建立了一种新的选择方法，用于使用代谢抑制剂（埃米森和放线菌素D）构建人T细胞杂交瘤。从由此建立的人T细胞杂交瘤克隆中，我们克隆了人光毒素的cDNA，并成功地产生了大量的重组人光毒素。在体外和体内实验中，发现重组人光毒素对恶性肿瘤细胞具有特异性的细胞毒性。在分析人光氧素体内抗肿瘤活性的过程中，我们发现人光氧素具有强的巨噬细胞趋化和巨噬细胞激活活性。从另一个人T细胞杂交瘤克隆H3-E9-6中，我们部分纯化了两种巨噬细胞活化因子。其中之一MAF-CI是与人干扰素不同的启动因子<gamma>。另一种是MAF-CII，它是一种不同于脂多糖的触发因子。这两种巨噬细胞活化因子对人单核细胞显示出协同作用，并诱导人单核细胞的强杀肿瘤活性。目前，我们正在对这两个因子进行全面的纯化和结构研究.人和小鼠巨噬细胞杂交瘤产生的单核因子：我们成功地建立了许多小鼠和人巨噬细胞杂交瘤，并分析了这些巨噬细胞杂交瘤产生的各种单核因子。建立的人巨噬细胞杂交瘤克隆之一被发现分泌一种有效的肿瘤特异性细胞毒素，其不同于人光毒素、肿瘤坏死因子和白细胞介素-1。