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Cancer Immunol Immunother. 2007 Nov;56(11):1733-42. Epub 2007 Apr 11.

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

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1
Department of Experimental Medicine, University of Genoa, Genoa, Italy.

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.

PMID:
17426969
DOI:
10.1007/s00262-007-0317-0
[Indexed for MEDLINE]
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