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PALABRAS CLAVE: Celulas Natural Killer (NK), Interleucina 15 (IL-15), tumores solidos refractarios. Kill the Killers: Natural Killer cells therapy against paediatric refractory solid tumours SUMMARY Introduction: Refractory solid tumours lead children deaths. To change this statement, new treatments should be developed. Natural Killer cells constitute the first line of defence against tumour cells. We propose a new strategy for antitumor cell therapy in children with refractory solid malignancies: IL-15 stimulated NK cells. Patients and methods: 22 paediatric patients suffering refractory solid tumours participate in this study. We compare NK cell subsets and K562 cytotoxicity in patients and sex-age pair's healthy controls. We use multiparametric flow and time-resolved fluorescent, respectively. In immunocompromised mice we developed an aggressive human metastatic neuroblasto- ma model and IL-15 stimulated NK cells rescue. Results: Patients had higher NK bright cells subset and lower NK cytotoxicity than healthy controls. IL-15 stimulated NK cells improved NK cell cytotoxicity in vitro and decreased tumour burden in vivo. Conclusions: IL-15 sti- mulated NK cells may constitute a new cell therapy tool for paediatric refractory tumours.

Kill the Killers: terapia con células Natural Killer en pacientes pediátricos con cáncer refractario