Fujiwara T, Sakagami K, Matsuoka J, Shiozaki S, Fujioka K, Takada Y, Uchida S, Onoda T, Orita K
First Department of Surgery, Okayama University Medical School, Japan.
Biotherapy. 1991;3(3):203-9. doi: 10.1007/BF02171683.
We evaluated the antitumor effect of an interleukin 2 (IL-2) slow delivery system, the IL-2 mini-pellet, in two murine solid tumor models, and also investigated the enhancement of its therapeutic effect by serial administration. The IL-2 mini-pellet contains 1 x 10(6) units of IL-2 and releases it slowly in vivo. In our experiment, the IL-2 mini-pellet was administered subcutaneously near the tumor site in combination with the intravenous injection of lymphokine-activated killer (LAK) cells. When this regimen was given on days 8 and 11 after the subcutaneous inoculation of Meth A fibrosarcoma into BALB/c mice, tumor growth was significantly inhibited (p less than 0.05) compared to tumor growth in untreated controls. Moreover, the IL-2 mini-pellet alone was also effective in inhibiting tumor growth. In another experiment, MH134 hepatoma was inoculated into C3H/He mice. Both administration of the IL-2 mini-pellet alone and in combination with LAK cells resulted in complete tumor regression in four of five mice. In a third experiment, serial administration of the IL-2 mini-pellet at 3- or 5-day intervals prolonged the suppression of Meth A fibrosarcoma growth in BALB/c mice. These results suggested that the IL-2 mini-pellet could be applied to cancer immunotherapy and that its antitumor effect could be prolonged by serial administration.
我们评估了白细胞介素2（IL-2）缓释系统——IL-2微丸在两种小鼠实体瘤模型中的抗肿瘤作用，并研究了通过连续给药增强其治疗效果的情况。IL-2微丸含有1×10⁶单位的IL-2，并在体内缓慢释放。在我们的实验中，将IL-2微丸皮下注射到肿瘤部位附近，并联合静脉注射淋巴因子激活的杀伤细胞（LAK细胞）。当在将Meth A纤维肉瘤皮下接种到BALB/c小鼠后的第8天和第11天给予该方案时，与未治疗的对照组相比，肿瘤生长受到显著抑制（p<0.05）。此外，单独使用IL-2微丸也能有效抑制肿瘤生长。在另一项实验中，将MH134肝癌接种到C3H/He小鼠体内。单独给予IL-2微丸以及与LAK细胞联合使用，在五只小鼠中有四只导致肿瘤完全消退。在第三项实验中，以3天或5天的间隔连续给予IL-2微丸可延长对BALB/c小鼠Meth A纤维肉瘤生长的抑制作用。这些结果表明，IL-2微丸可应用于癌症免疫治疗，并且通过连续给药可延长其抗肿瘤作用。
