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

Roberta Castriconi, Alessandra Dondero, Michele Cilli, Emanuela Ognio, Annalisa Pezzolo, Barbara De Giovanni, Claudio Gambini, Vito Pistoia, Lorenzo Moretta, Alessandro Moretta, Maria Valeria Corrias

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)1733-1742
Number of pages10
JournalCancer Immunology, Immunotherapy
Volume56
Issue number11
DOIs
Publication statusPublished - Nov 2007

Keywords

  • Immunotherapy
  • Metastasis
  • Neuroblastoma
  • NK cells
  • NOD/scid

ASJC Scopus subject areas

  • Cancer Research
  • Immunology
  • Oncology

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