Haploidentical Stem Cell Transplantation and IL-15 NK Cell Infusion for Paediatric Refractory Solid Tumours

Overview

The investigators propose a new antitumor cell therapy for treating childhood refractory solid tumours. The aim of this study is explore the graft versus tumour effect mediated by allogenic natural killer cells (NKs). NK cell alloreactivity can be predicted by donor killer immunoglobulin-like receptors (KIRs) and human leukocyte antigen (HLA) class I alleles mismatch. Cells without an inhibitory HLA ligand may trigger natural killer cell activation and elimination of those target cells. Reduced risk of relapsed has been described in malignant cancer after haploidentical stem cell transplantation when HLA ligands against the inhibitory KIRs present in the donor were absent in the recipient (KIR-HLA receptor-ligand mismatch). NK alloreactivity could also be obtained by Natural Killer Receptor (NCR), Toll-Like-Receptors (TLRs) and NKG2D receptor stimulation mediated by cytokines or tumour cell lines. This will be an open, non randomized, Phase I/II clinical trial, with a double objective: therapeutic exploratory. The investigators aim at studying safety and efficacy of haploidentical stem cell transplantation for the treatment of these malignancies with no cure known. Patients will receive an haploidentical stem cell transplantation, followed by IL-15 stimulated NK cells infusion one month after transplantation. Efficacy of the procedure will be evaluated with up-to-date radiological techniques, molecular studies and functional assays.

The investigators propose a new antitumor cell therapy for treating childhood refractory solid tumours. The aim of this study is explore the graft versus tumour effect mediated by allogenic natural killer cells (NKs). NK cell alloreactivity can be predicted by donor killer immunoglobulin-like receptors (KIRs) and human leukocyte antigen (HLA) class I alleles mismatch. Cells without an inhibitory HLA ligand may trigger natural killer cell activation and elimination of those target cells. Reduced risk of relapsed has been described in malignant cancer after haploidentical stem cell transplantation when HLA ligands against the inhibitory KIRs present in the donor were absent in the recipient (KIR-HLA receptor-ligand mismatch). NK alloreactivity could also be obtained by Natural Killer Receptor (NCR), Toll-Like-Receptors (TLRs) and NKG2D receptor stimulation mediated by cytokines or tumour cell lines.