title: Comparison of adherent lymphokine-activated killer (a-lak) cells generated by IL-2 and IL-7 - cellular modifications induced by IL-7.
abstract: At present, the clinical application of plastic-adherent-lymphokine-activated killer (A-LAK) cells shows limited success in the immunotherapy of patients with advanced cancer because of a low responder rate, severe side effects and failures in yielding sufficient numbers of cells for adoptive transfers. Since interleukin-7 (IL-7) is able to induce LAK activity independently of IL-2, we investigated the ability of IL-7 to improve the yield and the properties of A-LAK cells. A-LAK cells from 7 healthy donors generated in the presence of IL-2, IL-7 or combinations of IL-2 plus IL-7 (each 1000 U/ml) were compared with regard to plastic adherence, expansion rate, immunophenotype, cytokine secretion and cytotoxicity against malignant melanoma cells and non-malignant target cells. Our results demonstrate that A-LAK cells generated by a simultaneous stimulation of IL-2 plus IL-7 displayed a significantly higher expansion rate (10.7-fold vs. 9.0-fold), but showed no difference in the cytolytic activity compared to A-LAK cells generated by IL-2 alone. A-LAK cells generated by IL-7 alone demonstrated a low expansion rate (1.1-fold vs. 8.8-fold), and decreased in other properties like plastic adherence, CD56(+)/CD3(+) cell-ratio and cytolytic activity compared to A-LAK cells generated by IL-2 alone. A-LAK cells generated by IL-7 or a sequential stimulation of IL-2 and IL-7, on the other hand, exhibited a more selective cytotoxicity for malignant melanoma cells compared to the non-malignant keratinocyte target cell line (HaCaT) and normal fibroblasts. A sequential replacement of LL-2 by IL-7 might help to reduce the severe side effects of IL-2. In vivo experiments are necessary to evaluate the potential value of IL-7 in adoptive immunotherapy.
authors.affiliation: HUMBOLDT UNIV BERLIN,KLINIKUM RUDOLF VIRCHOW,DEPT DERMATOL,D-13353 BERLIN,GERMANY.
authors.forename: P
authors.initials: P
authors.lastname: Moller
authors.forename: M
authors.initials: M
authors.lastname: Bohm
authors.forename: S
authors.initials: S
authors.lastname: Krugerkrasagakes
authors.forename: C
authors.initials: C
authors.lastname: Kohlmus
authors.forename: M
authors.initials: M
authors.lastname: Artuc
authors.forename: B
authors.initials: B
authors.lastname: Czarnetzki
authors.forename: D
authors.initials: D
authors.lastname: Schadendorf