Joining the forces of Natural Killer Cells and Ferroptosis to treat Refractory Neuroblastoma

Neuroblastoma (NB), a rare paediatric solid tumour, accounts for 15% of childhood cancer deaths. Immunotherapy has improved the survival for haematological malignancies, but solid tumours remain a challenge.

The high heterogeneity, low mutational load, and strong immunosuppressive tumour microenvironment (i-TME) have hindered the success of immunotherapy in NB.

Recently, natural killer (NK) cells have stood as a promising immunotherapeutic tool, as they dont depend on specific mutations. Still, clinical trials for NB show only modest results, proving further action is needed to overcome the iTME.

Late findings show that refractory tumours often respond to Ferroptosis, a novel cell death mechanism that is highly immunogenic. Cancer cells undergoing ferroptosis release HMGB1 and other well-known recruiters of NK cells.

Moreover, ferroptotic drugs can act through several mechanisms and can be adapted to patients with different tumour characteristics.

The goal of IronKiller is to combine ferroptotic drugs with NK cell therapy to treat refractory NB, and to perform in silico modelling of the results to predict which patients would benefit from this novel therapy.I am an experienced biologist and engineer joining a clinical research group strong in immunotherapies.

We will follow an in vitro-in vivo-in silico strategy that will cover a variety of disciplines, from basic biology and pre-clinical research, all the way to bioinformatics and machine learning.

I will reinforce my experience in cell death mechanisms and translational research, and I will also acquire new knowledge and skills in the areas of cell immunotherapy and oncological mathematical modelling. The latter through a secondment at an academic institution.

Along with the research work, the diverse training, management and communication activities planned, will play a key role in advancing my professional development towards becoming an independent academic group leader in translational cancer research.