TARGETED CELLULAR CYTOTOXICITY

靶向细胞毒性

• 批准号: 3808592
• 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/3808592
• 关键词: CD3 molecule; T cell receptor; antitumor antibody; athymic mouse; cell mediated cytotoxicity; interferons; neoplasm /cancer immunology; ovary neoplasms; tumor necrosis factor alpha

1.Human PBL that are targeted with bispecific antibodies exhibit an antitumor activity mediated by cytokines secreted into the medium as a result of T cell receptor crosslinking. This activity is different from targeted cytolysis as measured by 5lCr release in that it leads to the eradication of both target and bystander tumor cells. Two cytokines involved in blocking tumor growth are TNF-alpha and IFN-gamma. Induced cytokine release may be a major means by which targeted lymphocytes block tumor growth in vivo. 2. Targeted human PBL were tested for the ability to block the growth of established human ovarian carcinoma in nude mice. When given 4 days after tumor, PBL coated with anti-CD3 containing bispecific antibodies greatly decreased the number of mice bearing observable tumor at day 15, and at least doubled the long term survival times of tumor bearing mice.

1.用双特异性抗体靶向的人PBL表现出与靶向的人PBL相似的特性。 由分泌到培养基中的细胞因子介导的抗肿瘤活性 T细胞受体交联的结果。 这项活动不同于 通过51 Cr释放测量的靶向细胞溶解，因为它导致 根除靶肿瘤细胞和旁观者肿瘤细胞。 两种细胞因子 参与阻断肿瘤生长的是TNF-α和IFN-γ。 诱导 细胞因子的释放可能是靶向淋巴细胞阻断 体内肿瘤生长。 2.测试靶向的人PBL阻断肿瘤细胞增殖的能力。 在裸鼠中建立的人卵巢癌的生长。 当给予4 在肿瘤后30天，用含有抗CD 3的双特异性抗体包被PBL， 抗体大大减少了可观察到的荷瘤小鼠的数量 在第15天，肿瘤的长期存活时间至少增加了一倍， 产鼠