Even though all classified as “cancer”, there are major differences in origin and progression between adult and pediatric tumors. In adult malignancies, mutations are acquired to escape recognition and destruction by the immune system. In many pediatric malignancies, however, the origin of the tumor rather than acquired immune resistance mechanisms is the cause of poor tumor recognition by the immune system. My vision is that maximal efficacy of immune- and cell therapy in pediatric tumors can only be achieved when we stop extrapolating findings from adult cancer and study therapies in pediatric context.
I focus on the development and optimization of pipelines to boost the in-house development of novel immunotherapy options for pediatric cancer. My research includes tumor-specific T-cell receptor (TCR) and chimeric antigen receptor (CAR) identification for (in-house identified) actionable targets for pediatric immunotherapy. In addition, I focus on the potential of engineered unconventional immune cells (e.g. NKT-cells, MR1-restricted T-cells, and (thymic) NK-cells) to fight pediatric cancer.
Besides this, I am continuing my PhD research into increasing T-cell recognition of neuroblastoma tumors to increase long-term outcome of immunotherapy. Neuroblastoma is “infamous” for their capacity to hide from the immune system. We observed that neuroblastoma tumors can switch their phenotype, and that this switch in cell lineage goes hand-in-hand with expression of markers required to be recognized by the immune system (like MHC-I). We found that treatment with a drug class called HDAC inhibitors induces this cell lineage switch and enhances recognition of neuroblastoma cells by various immune cells, including T- and NK-cells. We currently study this effect in more detail in vitro and in vivo to set the stage for combination approaches to increase immunotherapy efficacy.