Arinaga S, Karimine N, Takamuku K, Nanbara S, Inoue H, Abe R, Watanabe D, Asoh T, Ueo H, Akiyoshi T
Department of Surgery, Medical Institute of Bioregulation, Kyushu University, Japan.
Cancer Invest. 1994;12(6):588-96. doi: 10.3109/07357909409023043.
Based on our clinical findings that the ability of cancer patients to generate lymphokine-activated killer (LAK) cells was remarkably augmented after mitomycin C (MMC) administration, we designed a treatment regimen that consisted of MMC 12 mg/m2, i.v. on day 1 and recombinant interleukin-2 (IL-2) 700 U/m2, i.v. every 12 hr from day 4 through day 8. Of 29 patients with advanced carcinoma treated with this regimen, 10 had a partial response (PR) and 4 had a minor response. The correlation of hematological and immunological changes associated with this treatment with the antitumor response to this therapy was investigated. Pretreatment values of total white blood cell and lymphocyte counts, and the level of increase of eosinophil counts in responder patients who showed a PR, were significantly greater than those in nonresponder patients. However, there was no correlation between clinical response and cytotoxic activities of peripheral blood mononuclear (PBM) cells, including NK and LAK activity, and the ability to generate LAK cells after the treatment. The capacity of adherent cells in PBM to produce IL-1-beta was increased after the treatment in both responders and nonresponders, whereas IL-1-alpha production was not increased. In addition, a significant increase in the ability to produce TNF-alpha was observed only in responders, indicating the correlation of TNF-alpha production with clinical response to this therapy. Since these correlations had been reported in the previous studies using IL-2, the present results suggested that the therapeutic effectiveness of this therapy against advanced carcinoma, is due to IL-2 probably augmented by its combination with MMC. In addition, these parameters might be predictive of therapeutic efficacy of this treatment.
基于我们的临床发现，即丝裂霉素C（MMC）给药后癌症患者产生淋巴因子激活的杀伤（LAK）细胞的能力显著增强，我们设计了一种治疗方案，包括第1天静脉注射MMC 12 mg/m²，以及从第4天至第8天每12小时静脉注射重组白细胞介素-2（IL-2）700 U/m²。在接受该方案治疗的29例晚期癌患者中，10例有部分缓解（PR），4例有轻度缓解。研究了与该治疗相关的血液学和免疫学变化与该疗法抗肿瘤反应的相关性。显示PR的反应者患者的总白细胞和淋巴细胞计数的预处理值以及嗜酸性粒细胞计数的增加水平，显著高于无反应者患者。然而，临床反应与外周血单核细胞（PBM）的细胞毒性活性（包括NK和LAK活性）以及治疗后产生LAK细胞的能力之间没有相关性。治疗后，反应者和无反应者的PBM中贴壁细胞产生IL-1-β的能力均增加，而IL-1-α的产生未增加。此外，仅在反应者中观察到产生TNF-α的能力显著增加，表明TNF-α的产生与该疗法的临床反应相关。由于这些相关性在先前使用IL-2的研究中已有报道，目前的结果表明该疗法对晚期癌的治疗效果可能归因于IL-2与MMC联合使用可能增强了其作用。此外，这些参数可能预测该治疗的疗效。
