Gallinger S, Hoskin D W, Mullen J B, Wong A H, Roder J C
Division of Molecular Immunology and Neurobiology, Mount Sinai Hospital Research Institute, Toronto, Ontario, Canada.
Cancer Res. 1990 Apr 15;50(8):2476-80.
An experimental model of hepatic metastases in C57BL/6 mice was used to compare the antitumor effects of lymphokine-activated killer (LAK) cells, anti-CD3-activated T-cells (ATC), and anti-CD3 alone. Liver metastases were produced by in vivo passage of MCA-38-LD adenocarcinoma via the ileocolic vein. LAK cells and ATC were generated by 3-day in vitro incubation of spleen cells in interleukin 2 and anti-CD3, respectively. Percentage of tumor volume in livers was determined with a morphometric technique. With less than therapeutic LAK cell doses (0.5-1.0 x 10(7) cells), no effect was seen in mean (+SE, -SE) percentage of tumor volume of control [23.3 (29.3, 18.5)] compared to LAK cell-treated [21.6 (29.3, 15.9)] animals. The same number of ATC significantly reduced the mean percentage of tumor volume [2.7 (4.7, 1.4)] (P less than 0.005). High dose interleukin 2 also significantly decreased tumor volume. More strikingly, a single dose of anti-CD3 alone had a beneficial effect on mean percentage of tumor volume when given i.p. [1.0 (1.9, 0.4)] or i.v. [1.2 (1.7, 0.7)] (P less than 0.0003). A total of 33% of anti-CD3-treated mice had no detectable liver metastases. In 51Cr release assays, the cytotoxicity of ATC was shown to be partially mediated by nylon wool-adherent accessory cells. The effectiveness of anti-CD3 in this immunotherapy model suggests that a similar approach may be taken to immunotherapy of human malignancies, without the requirements for in vitro-generated killer cells or exogenously administered interleukin 2.
采用C57BL/6小鼠肝转移实验模型，比较淋巴因子激活的杀伤细胞（LAK细胞）、抗CD3激活的T细胞（ATC）及单独使用抗CD3的抗肿瘤效果。通过经回结肠静脉将MCA-38-LD腺癌进行体内传代来产生肝转移。LAK细胞和ATC分别通过在白细胞介素2和抗CD3中对脾细胞进行3天体外培养而产生。采用形态测量技术测定肝脏中肿瘤体积的百分比。给予低于治疗剂量的LAK细胞（0.5 - 1.0×10⁷个细胞）时，与接受LAK细胞治疗的动物[21.6（29.3，15.9）]相比，对照动物肝脏肿瘤体积的平均（+标准误， -标准误）百分比[23.3（29.3，18.5）]未见变化。相同数量的ATC显著降低了肿瘤体积的平均百分比[2.7（4.7，1.4）]（P＜0.005）。高剂量白细胞介素2也显著减小了肿瘤体积。更显著的是，单独腹腔注射[1.0（1.9，0.4）]或静脉注射[1.2（1.7，0.7）]单剂量抗CD3对肿瘤体积的平均百分比有有益作用（P＜0.0003）。总共33%接受抗CD3治疗的小鼠未检测到肝转移。在⁵¹Cr释放试验中，ATC的细胞毒性显示部分由尼龙毛黏附的辅助细胞介导。抗CD3在该免疫治疗模型中的有效性表明，对于人类恶性肿瘤的免疫治疗可能可以采用类似方法，而无需体外产生的杀伤细胞或外源性给予白细胞介素2。
