TARGETED CELLULAR CYTOTOXICITY

1.以双特异性抗体为靶点的人PBL表现出 分泌到培养上清液中的细胞因子介导的抗肿瘤活性 T细胞受体交联的结果。本练习不同于 通过5ICr释放测量的靶向细胞溶解，因为它导致 消灭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肿瘤坏死因子-α和干扰素-γ。诱导式 细胞因子的释放可能是靶向淋巴细胞阻断的主要途径 肿瘤在体内生长。 2.检测靶向人外周血淋巴细胞对人外周血单个核细胞生长的阻断作用 在裸鼠体内建立人卵巢癌模型。如果给予4天的时间 肿瘤后用抗CD3双特异性抗体包被的PBL 极大地减少了第15天可见肿瘤的小鼠数量， 并使荷瘤小鼠的长期存活时间至少翻了一番。

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 5ICr 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.