TARGETED CELLULAR CYTOTOXICITY

靶向细胞毒性

• 批准号: 5201004
• 负责人: D M SEGAL
• 金额: --
• 依托单位: DIVISION OF CANCER BIOLOGY AND DIAGNOSIS
• 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/5201004
• 关键词: CD antigens; T lymphocyte; antitumor antibody; breast neoplasms; cell mediated cytotoxicity; cytolysis; disease /disorder model; genetic manipulation; human tissue; hybrid antibody; interleukin 2; laboratory mouse; lung neoplasms; metastasis; natural killer cells; neoplasm /cancer immunotherapy; neoplasm /cancer transplantation; protein tyrosine kinase

1. A murine mammary carcinoma model has been used to test the ability of targeted syngeneic T cells to eradicate transplanted solid tumor lung metastases. When given to tumor bearing mice, a genetically engineered bispecific antibody retards the growth of tumors and prolongs survival of mice. 2. A genetically engineered single chain bispecific molecule has been produced in mammalian cells and in bacteria which specifically redirects mouse T cells to lyse target cells in vitro, at ng/ml levels. 3. CD44 becomes a cytotoxic triggering molecule on human NK cells after 24 hr stimulation with IL-2 or IL-12. CD44-dependent lysis involves both serine-threonine and tyrosine kinases, and activation of CD44 is accompanied by its binding to other proteins, including one that is tyrosine phosphorylated. Similar studies have shown that CD69 becomes a cytotoxic triggering molecule on subsets of PBL after 4 days activation.

1. 已使用小鼠乳腺癌模型来测试该能力 靶向同基因 T 细胞根除移植实体瘤 肺转移。 当给予携带肿瘤的小鼠时，基因 工程双特异性抗体可延缓肿瘤的生长 延长小鼠的存活时间。 2. 基因工程单链双特异性分子已被 在哺乳动物细胞和细菌中产生，特别是 重定向小鼠 T 细胞以在体外裂解靶细胞（ng/ml） 水平。 3. CD44成为人类NK细胞的细胞毒性触发分子 用 IL-2 或 IL-12 刺激 24 小时后。 CD44依赖性裂解 涉及丝氨酸-苏氨酸和酪氨酸激酶，并且激活 CD44 伴随着与其他蛋白质的结合，包括一种 即酪氨酸磷酸化。 类似的研究表明CD69 4 天后成为 PBL 子集上的细胞毒性触发分子 激活。