Böhm M, Möller P, Kalbfleisch U, Worm M, Czarnetzki B M, Schadendorf D
University Hospital Rudolf Virchow, Department of Dermatology, Free University of Berlin, Germany.
Br J Cancer. 1994 Jul;70(1):54-9. doi: 10.1038/bjc.1994.249.
In order to assess the potential of interleukin 7 (IL-7) as an immunotherapeutic agent in human melanoma, we have evaluated the in vitro activity of IL-7-induced lymphokine-activated killer (LAK) cells from patients with advanced melanoma against allogeneic and autologous melanoma cells. Peripheral blood lymphocytes (PBLs) from 14 patients with stage III melanoma were isolated and incubated in the presence of 1,000 U ml-1 IL-7 and 100 U ml-1 IL-2 for comparison. LAK-cell activity was determined by a 24 h cytotoxicity assay using MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide]. The activity of IL-7-induced LAK cells against two allogeneic melanoma cell lines was 32.7% (+/- 17.9) against SK-Mel-37 and 38.1% (+/- 12.5) against SK-Mel-23 at an effector-to-target (E/T) ratio of 20:1. The activity of IL-2-induced LAK cells was significantly higher against SK-Mel-37 (78 +/- 24.6%) and against SK-Mel-23 (73.5 +/- 19.7%). IL-7 and suboptimal doses of IL-2 (10 U ml-1) were found to have a co-stimulatory on lymphocyte proliferation as well as on LAK activity. Against autologous melanoma cells, the activity of IL-7- and IL-2-induced LAK cells did not differ significantly (55.8 +/- 25.6% versus 68.7 +/- 21.7% respectively). In two patients, IL-7-induced LAK-cell activity against autologous melanoma cells exceeded even that of IL-2 significantly (67% vs 35% and 95% vs 82%). Levels of tumour necrosis factor alpha (TNF-alpha) in the supernatants of LAK-cell cultures generated by IL-7 were lower than those of IL-2-generated LAK-cell cultures. These results suggest that IL-7 is a potential alternative to immunotherapy with IL-2 in terms of efficacy and possible side-effects and encourages pilot studies with IL-7 in melanoma patients.
为了评估白细胞介素7（IL-7）作为人黑色素瘤免疫治疗药物的潜力，我们评估了晚期黑色素瘤患者中IL-7诱导的淋巴因子激活的杀伤细胞（LAK细胞）对同种异体和自体黑色素瘤细胞的体外活性。分离出14例III期黑色素瘤患者的外周血淋巴细胞（PBL），并在1000 U/ml IL-7和100 U/ml IL-2存在下进行培养以作比较。使用MTT [3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐]通过24小时细胞毒性试验测定LAK细胞活性。在效应细胞与靶细胞（E/T）比例为20:1时，IL-7诱导的LAK细胞对两种同种异体黑色素瘤细胞系的活性分别为：对SK-Mel-37为32.7%（±17.9），对SK-Mel-23为38.1%（±12.5）。IL-2诱导的LAK细胞对SK-Mel-37（78±24.6%）和对SK-Mel-23（73.5±19.7%）的活性显著更高。发现IL-7和次优剂量的IL-2（10 U/ml）对淋巴细胞增殖以及LAK活性有协同刺激作用。针对自体黑色素瘤细胞，IL-7和IL-2诱导的LAK细胞活性无显著差异（分别为55.8±25.6%和68.7±21.7%）。在两名患者中，IL-7诱导的LAK细胞对自体黑色素瘤细胞的活性甚至显著超过IL-2诱导的LAK细胞活性（分别为67%对35%和95%对82%）。IL-7产生的LAK细胞培养上清液中肿瘤坏死因子α（TNF-α）水平低于IL-2产生的LAK细胞培养上清液。这些结果表明，就疗效和可能的副作用而言，IL-7是IL-2免疫治疗的潜在替代方案，并鼓励对黑色素瘤患者进行IL-7的初步研究。
