Human NK cell infusions prolong survival of metastatic human neuroblastoma-bearing NOD/scid mice
Human NK cell infusions prolong survival of metastatic human neuroblastoma-bearing NOD/scid mice
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DOI：
10.1007/s00262-007-0317-0
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发表时间：
2007-11-01
影响因子：
5.8
通讯作者：
Corrias, Maria Valeria
中科院分区：
文献类型：
--
作者：
Castriconi, Roberta;Dondero, Alessandra;Corrias, Maria Valeria
一些证据表明，NK细胞免疫治疗可能是一种成功的方法，在神经母细胞瘤（NB）患者难治性的常规治疗。然而，NK细胞输注的归巢性质、安全性和治疗功效需要在合适的临床前小鼠NB模型中进行评估。在此，在存在或不存在NK活化细胞因子的情况下，NK细胞输注的治疗功效已经在NOD/scid小鼠中建立的NB转移模型中进行了评估，在NOD/scid小鼠中，注射的NB细胞迅速到达所有典型的转移部位，包括骨髓。输注多克隆IL 2激活的NK细胞后，这些细胞散布到各种组织中，包括那些被转移性NB细胞定殖的组织。早期反复注射IL 2激活的NK细胞可显著延长NB荷瘤NOD/scid小鼠的平均生存时间，这与骨髓浸润减少有关。低剂量的重组人IL 2或IL 15可进一步增强治疗效果。我们的结果表明，如果在微小残留病环境下进行，基于NK的过继免疫治疗可以代表治疗适当选择的转移性NB患者的有价值的辅助治疗。
Several lines of evidence suggest that NK cell immunotherapy may represent a successful approach in neuroblastoma (NB) patients refractory to conventional therapy. However, homing properties, safety and therapeutic efficacy of NK cell infusions need to be evaluated in a suitable preclinical murine NB model.Here, the therapeutic efficacy of NK cell infusions in the presence or absence of NK-activating cytokines have been evaluated in a NB metastatic model set up in NOD/scid mice, that display reduced functional activity of endogenous NK cells.In NOD/scid mice the injected NB cells rapidly reached all the typical sites of metastatization, including bone marrow. Infusion of polyclonal IL2-activated NK cells was followed by dissemination of these cells into various tissues including those colonized by metastatic NB cells. The early repeated injection of IL2-activated NK cells in NB-bearing NOD/scid mice significantly increased the mean survival time, which was associated with a reduced bone marrow infiltration. The therapeutic effect was further enhanced by low doses of human recombinant IL2 or IL15.Our results indicate that NK-based adoptive immunotherapy can represent a valuable adjuvant in the treatment of properly selected NB patients presenting with metastatic disease, if performed in a minimal residual disease setting.