Loeffler C M, Platt J L, Anderson P M, Katsanis E, Ochoa J B, Urba W J, Longo D L, Leonard A S, Ochoa A C
Department of Surgery, University of Minnesota, Minneapolis 55455.
Cancer Res. 1991 Apr 15;51(8):2127-32.
The stimulation of murine splenocytes with the monoclonal antibody anti-CD3 and interleukin 2 (IL-2) results in the propagation of large numbers of cells (T-activated killer; T-AK) which demonstrate high therapeutic efficacy when infused with IL-2 into mice bearing pulmonary metastases. Interleukin 2 infusions are required to maintain the function of the adoptively transferred cells. Recent data demonstrate that the therapeutic efficacy can be enhanced by encapsulating IL-2 in liposomes. The present work tested the combination of T-AK cells with IL-2 liposomes in an immunotherapy model utilizing the MCA-38 murine colon adenocarcinoma. Expansion of murine splenocytes was achieved with anti-CD3 monoclonal antibody plus IL-2 and was consistently greater than 50-fold during a 9-day culture period. Cytolytic activity of the murine T-AK cells was mediated primarily by Lyt-2+ cells. In vivo results demonstrate synergistic therapeutic efficacy of the combination of IL-2 liposomes and T-AK cells. Evaluation of the in vivo distribution of these T-AK cells utilizing congenic mice demonstrates that Lyt-2+ cells from these in vitro cultures infiltrate hepatic metastases in vivo. The activation of lymphocytes with anti-CD3 monoclonal antibody and IL-2 appears to be a reproducible and convenient method of producing cells capable of producing antitumor effects in models of adoptive immunotherapy.
用抗CD3单克隆抗体和白细胞介素2（IL-2）刺激小鼠脾细胞可导致大量细胞增殖（T激活杀伤细胞；T-AK），当将其与IL-2一起注入患有肺转移瘤的小鼠体内时，显示出高治疗效果。需要输注白细胞介素2来维持过继转移细胞的功能。最近的数据表明，将IL-2包裹在脂质体中可提高治疗效果。本研究在利用MCA-38小鼠结肠腺癌的免疫治疗模型中测试了T-AK细胞与IL-2脂质体的组合。用抗CD3单克隆抗体加IL-2实现小鼠脾细胞的扩增，在9天的培养期内扩增始终大于50倍。小鼠T-AK细胞的细胞溶解活性主要由Lyt-2 +细胞介导。体内结果表明IL-2脂质体和T-AK细胞组合具有协同治疗效果。利用同源小鼠评估这些T-AK细胞的体内分布表明，来自这些体外培养物的Lyt-2 +细胞在体内浸润肝转移灶。用抗CD3单克隆抗体和IL-2激活淋巴细胞似乎是一种可重复且方便的方法，可在过继免疫治疗模型中产生能够产生抗肿瘤作用的细胞。
