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Invasive fungal disease (IFD) in hematopoietic stem cell transplantation is associatedwith high morbidity and mortality. As the antifungal host response determines risk and outcomeof IFD, there is growing interest in adoptive immunotherapy using T cells or natural killer (NK)cells. Although the NK-92 cell line has been tested as anticancer therapy in clinical trials, data onthe antifungal activity of NK-92 cells are lacking. Here, we show that the NK-92 cell line exhibitsconsiderable fungal damage on all medically important fungi tested, such as different species ofAspergillus,Candida, mucormycetes, andFusarium. The extent of fungal damage differs acrossvarious species of mucormycetes andFusarium, whereas it is comparable across different species ofAspergillusandCandida. Interferon (IFN)-γlevels in the supernatant were lower when NK-92 cells areco-incubated withAspergillus fumigatus,Candida albicans, orRhizopus arrhizuscompared to the levelswhen NK-92 cells are incubated alone. Different to primary human NK cells, no increase of perforinlevels in the supernatant was observed when the fungi were added to NK-92 cells. Ourin vitrodatademonstrated that the NK-92 cell line could be a feasible tool for antifungal immunotherapy, butdata of animal models are warranted prior to clinical trials.
The incidence of invasive mold disease (IMD) has significantly increased over the last decades, and IMD of the central nervous system (CNS) is a particularly severe form of this infection. Solid data on the incidence of CNS IMD in the pediatric setting are lacking, in which Aspergillus spp. is the most prevalent pathogen, followed by mucorales. CNS IMD is difficult to diagnose, and although imaging tools such as magnetic resonance imaging have considerably improved, these techniques are still unspecific. As microscopy and culture have a low sensitivity, non-culture-based assays such as the detection of fungal antigens (e.g., galactomannan or beta-D-glucan) or the detection of fungal nucleic acids by molecular assays need to be validated in children with suspected CNS IMD. New and potent antifungal compounds helped to improve outcome of CNS IMD, but not all agents are approved for children and a pediatric dosage has not been established. Therefore, studies have to rapidly evaluate dosage, safety and efficacy of antifungal compounds in the pediatric setting. This review will summarize the current knowledge on diagnostic tools and on the management of CNS IMD with a focus on pediatric patients.