过继性 NK 细胞输注作为肾母细胞瘤潜在治疗范式的临床前研究

Natural killer (NK) cell therapy has been shown to be effective in the treatment of some cancers. However, the effects of this adoptive immunotherapy have not been investigated for Wilms tumor (WT). In this study, the effects of adoptive NK-cell transfer on a patient-derived xenograft (PDX) model of anaplastic WT were evaluated, and the impacts of cell source and ex vivo activation strategy on the therapeutic efficacy of NK-cell product were appraised.

NK cells were isolated from human peripheral blood mononuclear cells (NK PB ) and human cord blood (NK CB ), and were expanded and activated using a cytokine cocktail. Another group of NK cells (NK ET ) was produced through activation with the exosomes extracted from previously challenged NK PB cells with WT. PDX-bearing mice were treated with clinically relevant doses of NK PB , NK CB , NK ET , standard chemotherapy, and placebo (phosphate-buffered saline).

PDX models treated with NK CB showed a better survival rate, though the difference among the study groups was not significant. Compared with the placebo control group, NK CB significantly improved the histopathologic response, NK PB significantly inhibited the proliferation of neoplastic cells, and NK ET led to a significant decrease in the metastasis score (all p-values <.05). Standard chemotherapy provided the greatest tumor growth inhibition and the lowest mitotic count, though it did not show any significant advantage over NK-cell therapies in any of the outcome parameters in two-by-two comparisons.

This study spotlights the efficacy of adoptive NK-cell transfer as a potential treatment candidate for high-risk WT.