ENGINEERING CELL TYPE SPECIFIC TOXINS

工程细胞类型特异性毒素

• 批准号: 6163023
• 负责人: R J YOULE
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6163023
• 关键词: AIDS therapy; CD4 molecule; antiAIDS agent; brain neoplasms; cytotoxicity; endoribonucleases; genetic manipulation; human tissue; immunoconjugates; immunotoxicity; molecular cloning; monoclonal antibody; neoplasm /cancer immunotherapy; neurotoxins; pancreatic ribonuclease; protein engineering; tumor antigens

Monoclonal antibodies selectively bind tumor cell differentiation antigens in vitro and in vivo. Since natural effector mechanisms often do not mediate killing of monoclonal antibody bound cells we have devised methods of linking extremely toxic proteins to the antibodies to selectively kill tumor cells. We have succeeded in developing several new approaches to apply immunotoxins in vivo. (1) Cloning toxins, then altering their structure at the gene level to decrease non target cell toxicity; (2) preparation of genetically engineered immunotoxins for clinical trials of human brain tumor patients; (3) prevention of an immune response against immunotoxins with anti-CD4 antibodies; (4) use of human cytotoxic proteins such as RNase linked to antibodies to selectively target cells; (5) understanding the mechanism of human RNase neurotoxins; and (6) discovering that RNases block HIV infection in vivo.

单克隆抗体选择性结合肿瘤细胞分化 体外和体内抗原。 由于自然效应机制通常 不介导杀死我们拥有的单克隆抗体结合细胞 设计了将剧毒蛋白质与抗体连接起来的方法 选择性地杀死肿瘤细胞。 我们已经成功开发了 几种在体内应用免疫毒素的新方法。 (1)克隆 毒素，然后在基因水平上改变其结构以减少非毒素 靶细胞毒性； (2)基因工程的制备 用于人脑肿瘤患者临床试验的免疫毒素； (3) 用抗 CD4 预防针对免疫毒素的免疫反应 抗体； (4)利用人类细胞毒性蛋白如RNase连接 选择性靶向细胞的抗体； (5) 理解 人类RNase神经毒素的作用机制； (6) 发现 RNase 阻断体内HIV感染。