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Allogeneic peripheral blood-derived natural killer (NK) cells (CD3- CD56+) are an adoptive cellular immunotherapy developed by the IRCCS Istituto Giannina Gaslini for the treatment of high-risk neuroblastoma. These cells are harvested from haploidentical donors, typically a parent, and undergo a purification process to deplete CD3+ T cells (to prevent graft-versus-host disease) and enrich CD56+ NK cells. The therapeutic effect is driven by the innate ability of NK cells to identify and lyse tumor cells that have downregulated MHC class I molecules or express stress-induced ligands. This activity is further enhanced in the haploidentical setting by KIR-ligand mismatch, where the donor's inhibitory killer cell immunoglobulin-like receptors (KIRs) do not recognize the recipient's HLA molecules, thus lowering the threshold for NK cell activation. In clinical protocols for neuroblastoma, these cells are often administered following lymphodepleting chemotherapy and in combination with cytokines like interleukin-2 (IL-2) or anti-GD2 monoclonal antibodies to trigger antibody-dependent cellular cytotoxicity (ADCC).
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