Ishikawa Eiichi, Tsuboi Koji, Takano Shingo, Uchimura Eiji, Nose Tadao, Ohno Tadao
Department of Neurosurgery, Institute of Clinical Medicine, University of Tsukuba, Tsukuba Science City, Ibaraki 305-8575, Japan.
Cancer Sci. 2004 Jan;95(1):98-103. doi: 10.1111/j.1349-7006.2004.tb03177.x.
Combined therapy with a fixed-tumor cell vaccine and intratumoral injection of NK cells induced strong tumor regression of rat glioma. Rat 9L glioma cells were inoculated into syngeneic male rats at the flank (subcutaneous tumor model) or at the basal ganglia of the right hemisphere (intracranial tumor model). Rats were intradermally injected three times with vaccine comprising fixed 9L cells, IL-2- and GMCSF-microparticles, and tuberculin prior to (protective studies) or after (therapeutic studies) challenge with live 9L cells. In the protective studies, the vaccine alone achieved significant tumor growth inhibition and elongation of mean life span in both the subcutaneous and intracranial tumor models. No therapeutic effect was observed in the intracranial tumor model with the vaccine alone. However, intratumoral injection of rat NK cells strongly assisted the therapeutic effect of the vaccine in the brain tumor model and resulted in a statistically significant elongation of life span. We propose that intratumoral injection of NK cells may not only kill brain tumor cells directly, but also trigger a strong immune response in the focal lesion of the brain after vaccination.
固定肿瘤细胞疫苗与瘤内注射NK细胞的联合疗法可诱导大鼠胶质瘤发生强烈的肿瘤消退。将大鼠9L胶质瘤细胞接种于同基因雄性大鼠的胁腹（皮下肿瘤模型）或右半球基底神经节（颅内肿瘤模型）。在接种活9L细胞之前（保护性研究）或之后（治疗性研究），给大鼠皮内注射三次疫苗，该疫苗包含固定的9L细胞、IL-2和GMCSF微粒以及结核菌素。在保护性研究中，单独使用疫苗在皮下和颅内肿瘤模型中均实现了显著的肿瘤生长抑制并延长了平均寿命。单独使用疫苗在颅内肿瘤模型中未观察到治疗效果。然而，瘤内注射大鼠NK细胞在脑肿瘤模型中有力地辅助了疫苗的治疗效果，并导致寿命在统计学上显著延长。我们提出，瘤内注射NK细胞不仅可以直接杀死脑肿瘤细胞，还可以在接种疫苗后在脑局部病灶引发强烈的免疫反应。
