Onishi S, Saibara T, Fujikawa M, Sakaeda H, Matsuura Y, Matsunaga Y, Yamamoto Y
First Department of Internal Medicine, Kochi Medical School, Japan.
Hepatology. 1989 Sep;10(3):349-53. doi: 10.1002/hep.1840100318.
Ten patients with hepatocellular carcinoma, three of whom had pulmonary metastasis, were treated with adoptive immunotherapy using autologous lymphokine-activated killer cells plus recombinant interleukin 2. Patients received 15 micrograms per day of recombinant interleukin 2 consecutively (for 14 to 64 days), from Day 7 prior to the first leukapheresis, and received 10(9) to 10(10) lymphokine-activated killer cells once or twice per week intravenously; the lymphokine-activated killer cells had been generated from mononuclear cells obtained through leukapheresis. Preadministration of recombinant interleukin 2 prior to the first leukapheresis resulted in a remarkable increase of lymphokine-activated killer activity in seven of nine cases in whom lymphokine-activated killer activity had been poorly inducible even at high concentrations of recombinant interleukin 2. At the end of the treatment, liver tumor regression (34 and 63%, respectively, of two-dimensional size) was observed in two of two patients with a solitary tumor; no increase of liver tumor size was observed in seven patients with massive or multiple tumors, and no changes in the size or number of pulmonary metastatic tumors in any patients were observed. More than a 35% decrease in serum alpha-fetoprotein level was noted in four of nine alpha-fetoprotein-positive patients. However, Child's grades, performance status and lymphokine-activated killer activity on entry into the study could not be used as parameters to predict therapy responsiveness. Neither serious side effects nor significant changes of serum bilirubin, ALT and creatinine were noted. Thus, this treatment seems to be well tolerated even in advanced hepatocellular carcinoma with poor liver function reserve, and tumor regression could be expected in small-burden hepatocellular carcinoma. The assessment of the therapeutic effects and application in hepatocellular carcinoma awaits the development of this trial.
10例肝细胞癌患者接受了自体淋巴因子激活的杀伤细胞加重组白细胞介素2的过继性免疫治疗，其中3例有肺转移。患者从首次白细胞单采前7天开始连续每日接受15微克重组白细胞介素2（共14至64天），并每周静脉注射10⁹至10¹⁰个淋巴因子激活的杀伤细胞1至2次；淋巴因子激活的杀伤细胞由通过白细胞单采获得的单核细胞产生。在首次白细胞单采前给予重组白细胞介素2，使得9例即使在高浓度重组白细胞介素2时淋巴因子激活的杀伤活性也难以诱导的患者中，有7例的淋巴因子激活的杀伤活性显著增加。治疗结束时，2例孤立性肿瘤患者的肝肿瘤缩小（二维大小分别缩小34%和63%）；7例有大块或多发肿瘤的患者未观察到肝肿瘤大小增加，且所有患者的肺转移瘤大小和数量均无变化。9例甲胎蛋白阳性患者中有4例血清甲胎蛋白水平下降超过35%。然而，入组研究时的Child分级、体能状态和淋巴因子激活的杀伤活性不能作为预测治疗反应性的参数。未观察到严重副作用，血清胆红素、谷丙转氨酶和肌酐也无显著变化。因此，即使在肝功能储备差的晚期肝细胞癌患者中，这种治疗似乎也耐受性良好，对于小负荷肝细胞癌有望出现肿瘤缩小。该治疗效果的评估及其在肝细胞癌中的应用有待本试验的进一步开展。
