Human NK cell infusions prolong survival of metastatic human neuroblastoma-bearing NOD/scid mice

Cancer Immunol Immunother. 2007 Nov;56(11):1733-42. doi: 10.1007/s00262-007-0317-0. Epub 2007 Apr 11.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / immunology
  • Disease Models, Animal
  • Humans
  • Immunotherapy*
  • Killer Cells, Natural / immunology
  • Killer Cells, Natural / transplantation*
  • Mice
  • Mice, Inbred NOD
  • Mice, SCID
  • Neoplasm Metastasis / immunology
  • Neuroblastoma / immunology
  • Neuroblastoma / therapy*
  • Survival Rate
  • Transplantation, Heterologous


  • Antineoplastic Agents