MONOCLONAL ANTIBODY-TOXIN CONJUGATES FOR TUMOR THERAPY IN VIVO

用于体内肿瘤治疗的单克隆抗体-毒素缀合物

• 批准号: 3760264
• 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/3760264
• 关键词: CD4 molecule; Macaca mulatta; brain neoplasms; cerebellar Purkinje cell; cytotoxicity; drug administration routes; genetic manipulation; guinea pigs; human subject; human tissue; immunoconjugates; laboratory rat; 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) intrathecal administration of immunotoxins for therapy of brain tumors that kill 2-5 logs of tumor cells in animal models; (3) preparation of genetically engineered immunotoxins for clinical trials of human brain tumor patients; (4) prevention of an immune response against immunotoxin with anti-CD4 antibodies; (5) specific deletion of Purkinje cells in rats, guinea pigs, and rhesus monkeys; (6) use of human cytotoxic proteins such as RNase linked to antibodies to selectively target cells; and (7) understanding the mechanism of human RNase neurotoxins.

单克隆抗体选择性结合肿瘤细胞分化