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Inhibitors of cytotoxic T cell activities produced by cultured tumor cells.

培养的肿瘤细胞产生的细胞毒性 T 细胞活性抑制剂。

基本信息

批准号：
03454466
负责人：
TAKADA Kazuaki
金额：
$ 2.56万
依托单位：
HIROSHIMA UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1991
资助国家：
日本
起止时间：
1991 至 1992
项目状态：
已结题

项目摘要

It has been reported that patients with malignant tumors have a defective cellularimmune status. We have speculated that this defect was resulted from the production of soluble immuno-suppressive factors produced by tumor cells.We have established serum-free culture system to induce highly cytotoxic lymphokine activated killer (LAK)cells. Using this system, we have studied several growth factors, hormons and medium conditioned by several tumor cells on the growth and cytotoxic activities of LAK cells. Following results were obtained.1. The LAK cells induced in RD medium supplemented with interleukin-2, human transferrin, 2-mercaptoethanol, 2-aminoethanol and sodium selenite had 3 to 4 times higher cytotoxic activities against tumor cells than the LAK cells in human serum supplemented medium.2. Insulin or insulin like growth factor-I(IGF-I) which has been produced by many tumor cells as an autocrine or a paracrine growth factor inhibited cytotoxic activities of LAK cells.3. Transforming growth factor-beta (TGF-beta) inhibited both of the growth and cytotoxic activities of LAK cells.4. The medium conditioned by cultured squamous carcinoma cells (SCC) and malignant melanoma cells(MM) derived from oral region inhibited both of the growth and cytotoxic activities of LAK cells.5. Physical and chemical analysis revealed that the suppressive activities of SCC were heat- and acid-resistant but those of MM were heat- and acid-labile. These results suggest that the activities of SCC were different from those of MM.6. We have fractionated SCC derived activities by heparin-sepharose affinity chromatography. It has been revealed that the fractions which were eluted with 0.9-1.2M NaCl exhibited significant activities which were different from TGF-beta and insulin.

据报道，恶性肿瘤患者的细胞免疫状态存在缺陷。我们建立了无血清培养体系，诱导出具有高细胞毒活性的LAK细胞。利用该系统，我们研究了几种生长因子、β-内酰胺酶和几种肿瘤细胞条件培养液对LAK细胞生长和杀伤活性的影响。主要研究结果如下：1.结论：1.在含白细胞介素-2、人转铁蛋白、2-巯基乙醇、2-氨基乙醇和亚硒酸钠的RD培养基中诱导的LAK细胞对肿瘤细胞的杀伤活性是含人血清培养基中LAK细胞的3 ~ 4倍.许多肿瘤细胞产生的胰岛素或胰岛素样生长因子-I（IGF-I）作为一种自分泌或旁分泌的生长因子抑制LAK细胞的细胞毒活性.转化生长因子-β（TGF-β）抑制LAK细胞的生长和细胞毒活性.口腔鳞癌细胞（SCC）和口腔恶性黑色素瘤细胞（MM）条件培养液对LAK细胞的生长和杀伤活性均有抑制作用.理化分析表明，SCC的抑制活性是耐热和耐酸的，而MM的抑制活性是耐热和耐酸的。这些结果表明，SCC的活动是不同的MM。我们已经分馏SCC衍生活动肝素琼脂糖亲和层析。经0.9-1.2M NaCl洗脱的组分显示出明显的活性，其活性不同于TGF-β和胰岛素。