Therapeutic efficacy of ex vivo expanded allogeneic natural killer cells in mouse neuroblastoma model

      Natural killer (NK) cells are specialized lymphocytes that provide a first line of defense against viral infections and cancer. The therapeutic role of allogeneic NK cells has been shown in the setting of haploidentical hematopoietic stem cell transplantation. In the present study, we assessed anti-tumor efficacy of ex vivo-expanded allogeneic NK cells in mouse model to investigate the potential of therapeutic application of allogeneic NK cells from MHC-mismatched unrelated donor. Splenocytes from C57BL/6 mice were stimulated and expanded in the presence of IL-15 for 6 days. Compared with resting NK cells, these enriched NK cells displayed activated phenotype, efficiently produced cytokines, such as IFN-γ and TNF-α, and showed potent cytoxicity against various tumor cell lines. Therapeutic efficacy of expanded NK cells was evaluated in A/J mice injected with Neuro-2a mouse neuroblastoma cells. The progression of subcutaneously transplanted neuroblastoma was significantly suppressed by intratumoral injection of ex vivo-expanded NK cells. Of note, recurrence after surgical resection of tumor mass was efficiently controlled by intravenous injection of ex vivo-expanded allogeneic NK cells. In conclusion, ex vivo-expanded allogeneic NK cells demonstrated potent anti-tumor efficacy and have the potential for therapeutic application to treat measurable tumor burden and minimal residual disease as well.
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