Pediatric Cell and Gene Therapy Research Center, Gene, Cell & Tissue Research Institute, Tehran University of Medical Sciences, Tehran, Iran.
Gene Therapy Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran.
Pediatr Blood Cancer. 2022 Aug;69(8):e29676. doi: 10.1002/pbc.29676. Epub 2022 Apr 20.
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 ) and human cord blood (NK ), and were expanded and activated using a cytokine cocktail. Another group of NK cells (NK ) was produced through activation with the exosomes extracted from previously challenged NK cells with WT. PDX-bearing mice were treated with clinically relevant doses of NK , NK , NK , standard chemotherapy, and placebo (phosphate-buffered saline).
PDX models treated with NK showed a better survival rate, though the difference among the study groups was not significant. Compared with the placebo control group, NK significantly improved the histopathologic response, NK significantly inhibited the proliferation of neoplastic cells, and NK 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.
自然杀伤 (NK) 细胞疗法已被证明在治疗某些癌症方面有效。然而，这种过继免疫疗法对肾母细胞瘤 (WT) 的疗效尚未得到研究。在这项研究中，评估了过继性 NK 细胞转移对 WT 间变性 PDX 模型的影响，并评估了细胞来源和体外激活策略对 NK 细胞产品治疗效果的影响。
从人外周血单核细胞 (NK) 和人脐血 (NK) 中分离 NK 细胞，并使用细胞因子鸡尾酒进行扩增和激活。另一组 NK 细胞 (NK) 通过用 WT 细胞预先挑战的 NK 细胞提取的外泌体激活产生。用临床相关剂量的 NK、NK、NK、标准化疗和安慰剂（磷酸盐缓冲盐水）治疗携带 PDX 的小鼠。
接受 NK 治疗的 PDX 模型的存活率更好，但研究组之间的差异没有统计学意义。与安慰剂对照组相比，NK 显著改善了组织病理学反应，NK 显著抑制了肿瘤细胞的增殖，NK 导致转移评分显著降低（所有 p 值均 <.05）。标准化疗对肿瘤生长的抑制作用最大，有丝分裂计数最低，但与 NK 细胞疗法相比，在任何两两比较的结果参数中都没有显示出任何显著优势。
本研究强调了过继性 NK 细胞转移作为高危 WT 潜在治疗候选物的疗效。
