Abstract
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.
Highlights
Cv tokinesHuman recombinant interleukin 7 (IL-7) was provided by Immunex (Seattle, WA, USA) with a specific activity of 4.7 x 10' U mg-' and 3.9 endotoxin units per ng of protein
Smmuary 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
Immunotherapy with IL-2 with or without LAK cells has achieved some impressive regressions in patients with advanced melanoma who had failed on conventional therapy (Rosenberg et al, 1985; Fletcher et al, 1987)
Summary
Human recombinant IL-7 was provided by Immunex (Seattle, WA, USA) with a specific activity of 4.7 x 10' U mg-' and 3.9 endotoxin units per ng of protein. The specific activity was determined with a bioassay that employs the IL-7-dependent IxN/Lb pre-B-cell line (Namen et al, 1988). Human recombinant IL-2 was purchased from Boehringer (Mannheim, Germany) and had a specific activity of 2 x 106 U mg-' and fewer than 100 endotoxin units per ng
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