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01.11.2007 | Original Article

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

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

Erschienen in: Cancer Immunology, Immunotherapy | Ausgabe 11/2007

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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.

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Titel: Human NK cell infusions prolong survival of metastatic human neuroblastoma-bearing NOD/scid mice
verfasst von: Roberta Castriconi
Alessandra Dondero
Michele Cilli
Emanuela Ognio
Annalisa Pezzolo
Barbara De Giovanni
Claudio Gambini
Vito Pistoia
Lorenzo Moretta
Alessandro Moretta
Maria Valeria Corrias
Publikationsdatum: 01.11.2007
Verlag: Springer-Verlag
Erschienen in: Cancer Immunology, Immunotherapy / Ausgabe 11/2007
Print ISSN: 0340-7004
Elektronische ISSN: 1432-0851
DOI: https://doi.org/10.1007/s00262-007-0317-0

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

Abstract