ENGINEERING CELL TYPE SPECIFIC TOXINS

工程细胞类型特异性毒素

• 批准号: 6290634
• 负责人: RICHARD 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/6290634
• 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. We have devised methods of linking extremely toxic proteins to the antibodies to selectively kill tumor cells. (1) By cloning the toxins and mutating them to decrease non- target cell toxicity we have greatly increased the therapeutic specificity for tumor cells. (2) By the use of human cytotoxic proteins such as RNase linked to antibodies we have decreased the immune response of the recipient to the targeted toxins. 3) To improve this method of therapy of brain tumors we have prevented nonspecific toxicity to the vasculature by systemic delivery of chloroquine (4) We have developed new ways to target tumor cells to initiate programmed cell death. 5) We have explored the use of this technology to treat dystonia and muscle spasm disorders. - diphtheria toxin brain tumors immunotoxin monoclonal antibody ribonuclease RNases

单克隆抗体在体外和体内选择性结合肿瘤细胞分化抗原。我们已经设计出将剧毒蛋白质连接到抗体上的方法，以选择性地杀死肿瘤细胞。(1)通过克隆毒素并使其突变以降低非靶细胞毒性，我们大大提高了对肿瘤细胞的治疗特异性。(2)通过使用与抗体连接的人细胞毒性蛋白如RNA酶，我们已经降低了受体对靶毒素的免疫应答。3)为了改善这种治疗脑肿瘤的方法，我们已经通过全身递送氯喹来防止对脉管系统的非特异性毒性（4）我们已经开发了靶向肿瘤细胞以启动程序性细胞死亡的新方法。5)我们已经探索了使用这种技术来治疗肌张力障碍和肌肉痉挛疾病。- 白喉毒素脑肿瘤免疫毒素单克隆抗体核糖核酸酶