Takahashi K, Harauchi D, Kimura S, Saito S, Monden Y
University of Tokushima, School of Medicine, Japan.
Int J Immunopharmacol. 1998 Aug;20(8):375-88. doi: 10.1016/s0192-0561(98)00011-3.
We examined the effect of OK-432 on induction of cytotoxic T lymphocytes (CTL) directed against autologous tumor cells (ATC) and lymphokine-activated killer (LAK) cells from mononuclear cells separated from regional lymph node cells (RLMNCs) of 49 lung cancer patients. We also examined the phenotypic changes of RLMNCs during incubation with or without OK-432. Significant CTL activity and LAK activity against ATC developed from RLMNCs after stimulation with OK-432 or IL-2. Sequential treatment with OK-432 plus IL-2 or IL-2 plus OK-432 also developed significant CTL activity and LAK activity from RLMNCs. The CTL activity produced by OK-432 alone was as high as the CTL activity developed by IL-2 alone, OK-432 plus IL-2, or IL-2 plus OK-432. There was no significant difference in the CTL activities achieved by these four treatments. The proportion of CD25+ cells in RLMNCs after incubation with OK-432 was twice that before incubation. Although OK-432 increased IL-2 receptor expression on RLMNCs, it showed no synergistic effect with IL-2 in developing CTL and LAK activity. After incubation with OK-432, the proportion of HLA-DR + cells was also increased significantly. Moreover, the proportions of HLA-ABC+ and HLA-DR+ (class I and class II major histocompatibility complex antigens) cells in ATC were significantly larger than in Daudi cells. OK-432 alone could develop CTL activity against ATC from the RLMNCs of lung cancer patients that was as high as that developed by IL-2 alone or by sequential treatment with OK-432 plus IL-2 or IL-2 plus OK-432. The CTL developed from the RLMNCs of lung cancer patients may recognize class I and/or II antigens on the surface of ATC. These results indicated that treatment with OK-432 might be therapeutically useful for lung cancer patients as a CTL inducer rather than a LAK inducer.
我们研究了溶链菌制剂（OK-432）对诱导细胞毒性T淋巴细胞（CTL）的作用，这些CTL针对的是来自49例肺癌患者区域淋巴结细胞（RLMNCs）分离出的单核细胞中的自体肿瘤细胞（ATC）和淋巴因子激活的杀伤（LAK）细胞。我们还研究了在有或无OK-432孵育期间RLMNCs的表型变化。用OK-432或白细胞介素-2（IL-2）刺激后，RLMNCs产生了针对ATC的显著CTL活性和LAK活性。用OK-432加IL-2或IL-2加OK-432进行序贯治疗也使RLMNCs产生了显著的CTL活性和LAK活性。单独使用OK-432产生的CTL活性与单独使用IL-2、OK-432加IL-2或IL-2加OK-432产生的CTL活性一样高。这四种治疗方法所达到的CTL活性没有显著差异。用OK-432孵育后，RLMNCs中CD25+细胞的比例是孵育前的两倍。虽然OK-432增加了RLMNCs上IL-2受体的表达，但在产生CTL和LAK活性方面它与IL-2没有协同作用。用OK-432孵育后，HLA-DR +细胞的比例也显著增加。此外，ATC中HLA-ABC+和HLA-DR+（I类和II类主要组织相容性复合体抗原）细胞的比例明显大于Daudi细胞。单独使用OK-432就能产生针对肺癌患者RLMNCs中ATC的CTL活性，其水平与单独使用IL-2或用OK-432加IL-2或IL-2加OK-432序贯治疗产生的CTL活性一样高。从肺癌患者的RLMNCs产生的CTL可能识别ATC表面的I类和/或II类抗原。这些结果表明，作为一种CTL诱导剂而非LAK诱导剂，用OK-432治疗可能对肺癌患者具有治疗作用。
