ENGINEERING CELL TYPE SPECIFIC TOXINS

工程细胞类型特异性毒素

• 批准号: 2579557
• 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/2579557
• 关键词: AIDS therapy; CD4 molecule; antiAIDS agent; brain neoplasms; cytotoxicity; 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 immunotoxin with anti-CD4 antibodies; (4) use of human cytotoxic proteins such as RNase linked to antibodies to selectively target cells; and (5) understanding the mechanism of human RNase neurotoxins; 6) Discovering that RNases block HIV infection in vivo.

单抗选择性结合肿瘤细胞分化 体外和体内的抗原。由于自然效应器机构通常 不要干预我们设计的单抗结合细胞的杀伤 将剧毒蛋白与抗体连接起来的方法 选择性地杀死肿瘤细胞。我们已经成功地开发了几个 体内应用免疫毒素的新方法。(1)克隆毒素，然后 在基因水平上改变它们的结构以减少非靶细胞 毒性；(2)基因工程免疫毒素的制备 人脑肿瘤患者的临床试验；(3)预防 用抗CD4抗体对免疫毒素的免疫反应； 人细胞毒蛋白，如与抗体相连的核糖核酸酶 选择性靶细胞；以及(5)了解人类免疫缺陷的机制。 核糖核酸酶神经毒素；6)发现核糖核酸酶阻断HIV感染 活着。