AIM: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.
AIM: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.
Authors: Jeffrey M Venstrom; Junting Zheng; Nabila Noor; Karen E Danis; Alice W Yeh; Irene Y Cheung; Bo Dupont; Richard J O'Reilly; Nai-Kong V Cheung; Katharine C Hsu Journal: Clin Cancer Res Date: 2009-11-24 Impact factor: 12.531
Authors: Petter S Woll; Bartosz Grzywacz; Xinghui Tian; Rebecca K Marcus; David A Knorr; Michael R Verneris; Dan S Kaufman Journal: Blood Date: 2009-04-13 Impact factor: 22.113
Authors: Emily L Williams; Stuart N Dunn; Sonya James; Peter W Johnson; Mark S Cragg; Martin J Glennie; Juliet C Gray Journal: Clin Cancer Res Date: 2013-05-06 Impact factor: 12.531
Authors: B Marengo; C G De Ciucis; R Ricciarelli; A L Furfaro; R Colla; E Canepa; N Traverso; U M Marinari; M A Pronzato; C Domenicotti Journal: Cell Death Dis Date: 2013-04-11 Impact factor: 8.469