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


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.


CONCLUSIONS
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.
Castriconi
Roberta
R
Department of Experimental Medicine, University of Genoa, Genoa, Italy.
Dondero
Alessandra
A
Cilli
Michele
M
Ognio
Emanuela
E
Pezzolo
Annalisa
A
De Giovanni
Barbara
B
Gambini
Claudio
C
Pistoia
Vito
V
Moretta
Lorenzo
L
Moretta
Alessandro
A
Corrias
Maria Valeria
MV
D000818:Animals; D000970:Antineoplastic Agents / Q000276:immunology; D004195:Disease Models, Animal; D006801:Humans; D007167:Immunotherapy; D007694:Killer Cells, Natural / Q000276:immunology / Q000637:transplantation*; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009362:Neoplasm Metastasis / Q000276:immunology; D009447:Neuroblastoma / Q000276:immunology / Q000628:therapy*; D015996:Survival Rate; D014183:Transplantation, Heterologous
D000970:Antineoplastic Agents