Kohgo Y
Gan To Kagaku Ryoho. 1987 Jun;14(6 Pt 2):2127-34.
IL-2-activated killer cells (LAK cells) are potent effectors of adoptive immunotherapy in advanced cancer patients. We have undertaken fundamental experiments and a clinical pilot study in order to search for an efficient way of applying this therapy. Characterization of LAK cells: Human peripheral blood lymphocytes were fractionated by Ficoll-Isopaque and Percoll gradient centrifugation. The main activity was located in the low-density fraction (less than 1.061 g/ml), which corresponded to the LGL/NK fraction. However, the behavior of LAK cells against metabolic inhibitors such as DMSO, NDGA, EtOH and NaN3 was quite different from that of NK cells. LAK cells are resistant to lipoxygenation inhibitors and are labile to mitochondrial oxidation inhibitor, opposite to the behavior of NK. All the fractions sorted by FACS using CD16 and CD3 expressed LAK activity. This phenomenon was missed because LAK cells are sensitive to NaN3 which is usually contained in buffers of MoAb and in the running solution of cell sorter. Simulation study: The side effects and efficacy of LAK transfer were evaluated using Meth A sarcoma cell-bearing BALB/c mice. No side effects were observed and significant efficacy was obtained in mice whose tumors were located in the lung or abdominal cavity. Human pilot study: The pilot study was conducted in 25 patients with advanced carcinomas. Therapeutic efficacy was obtained in patients for whom local transfer was undertaken rather than systemic administration.
白细胞介素-2激活的杀伤细胞（LAK细胞）是晚期癌症患者过继性免疫治疗的有效效应细胞。我们进行了基础实验和临床初步研究，以寻找应用这种治疗方法的有效途径。LAK细胞的特性：人外周血淋巴细胞通过Ficoll-泛影葡胺和Percoll梯度离心进行分离。主要活性位于低密度组分（小于1.061 g/ml），这与淋巴细胞/自然杀伤细胞组分相对应。然而，LAK细胞对二甲基亚砜、去甲二氢愈创木酸、乙醇和叠氮化钠等代谢抑制剂的反应与自然杀伤细胞截然不同。LAK细胞对脂氧化抑制剂有抗性，对线粒体氧化抑制剂敏感，这与自然杀伤细胞的行为相反。使用CD16和CD3通过荧光激活细胞分选术分选的所有组分均表现出LAK活性。由于LAK细胞对通常存在于单克隆抗体缓冲液和细胞分选仪运行液中的叠氮化钠敏感，所以这一现象被忽视了。模拟研究：使用携带Meth A肉瘤细胞的BALB/c小鼠评估LAK细胞输注的副作用和疗效。未观察到副作用，并且在肿瘤位于肺部或腹腔的小鼠中获得了显著疗效。人体初步研究：对25例晚期癌症患者进行了初步研究。对进行局部输注而非全身给药的患者获得了治疗效果。
