Barr I G, Buchegger F, MacDonald H R, Carrel S, von Fliedner V
Ludwig Institute for Cancer Research, Lausanne Branch, Epalinges, Switzerland.
Cancer Detect Prev. 1988;12(1-6):439-50.
The specificity and efficiency of tumor cell lysis by the retargeting of murine and human cytolytic T lymphocytes (CTL) with heteroaggregated (also known as bispecific or hybrid) antibodies were examined. Both murine and human CTL were capable of lysing various tumor cell targets in the presence of low concentrations of an appropriate heteroaggregated antibody. However, CTL (excluding clones) were lytic only when activated using reagents such as concanavalin A and interleukin 2 (IL2) with murine effector cells and with mitogenic mAb with human effector cells. The addition of IL2 (at 50-100 U/ml) did not cause enhanced lysis of the target cells used in the presence of heteroaggregated antibody with the murine effector cells. Furthermore, the lysis of target cells by heteroaggregated antibodies and CTL did not cause the lysis of bystander cells (cells not expressing an antigen recognized by the antibody that are mixed with the target cells). The efficient CTL-mediated lysis observed with these antibodies makes this a promising approach for the immunotherapy of human cancer.
研究了用异源聚集（也称为双特异性或杂交）抗体重新靶向鼠和人细胞毒性T淋巴细胞（CTL）对肿瘤细胞的裂解特异性和效率。在低浓度的合适异源聚集抗体存在下，鼠和人CTL均能够裂解各种肿瘤细胞靶标。然而，CTL（不包括克隆）仅在使用诸如伴刀豆球蛋白A和白细胞介素2（IL2）等试剂激活鼠效应细胞以及使用促有丝分裂单克隆抗体激活人效应细胞时才具有裂解活性。添加IL2（50-100 U/ml）并不会增强在异源聚集抗体存在下与鼠效应细胞一起使用时靶细胞的裂解。此外，异源聚集抗体和CTL对靶细胞的裂解不会导致旁观者细胞（与靶细胞混合的不表达抗体识别抗原的细胞）的裂解。用这些抗体观察到的高效CTL介导的裂解使其成为人类癌症免疫治疗的一种有前景的方法。
