Do you want to make an impact? We are seeking a curious and passionate (tumor)immunologist, to unravel resistance to immunotherapy in children with B-cell precursor acute lymphoblastic leukemia.
B-cell precursor acute lymphoblastic leukemia (BCP-ALL) is the most common childhood cancer with ~100 newly diagnosed children yearly in the Netherlands and approximately 3,000 new cases in Europe. Patients receive risk-adapted combination chemotherapy for 2 up to 3 years, which cures more than 90% of patients in the modern era. For pediatric patients the intensive treatment schedule for several years is accompanied by co-morbidity and may impact quality of life, sometimes extending into adulthood.
Cell-based immunotherapy using the CD19xCD3 bispecific T cell engaging antibody blinatumomab is targeted to BCP-ALL cells and may induce less, or more manageable, off-target effects than conventional chemotherapeutics. However, using ex vivo assays we noticed that a substantial number of bone marrow aspirates taken from newly diagnosed BCP-ALL patients seems to be resistant to blinatumomab. Some of these cases appear to be initially immunosuppressed, while other cases display intrinsic cellular resistance. You will work to identify causes of this resistance in BCP-ALL using both molecular and cellular technologies. We aim to identify candidate genes and pathways for laboratory studies addressing functional causality with immunotherapy response and improvements thereof. Which, upon pre-clinical validation, will be assessed for prognostic and/or therapeutic value in patients.
The research group of prof. dr. Monique den Boer (currently comprising ~13 scientific personnel) focusses on identifying features of leukemic cells that can be used to improve the clinical outcome for children with BCP-ALL. We have expertise in pathobiological studies addressing the impact of leukemia-associated genetic alterations/drivers, how these lesions functionally contribute to response or non-response to therapeutic agents and their interaction with the bone marrow microenvironment. The Den Boer group routinely uses many molecular techniques, including (single cell) sequencing, CRISPR gene editing, conventional and spectral flow cytometry, confocal and spatial imaging, and organ-on-chip cell migration assays. Our 30-year track record in preclinical/translational childhood leukemia research has directly resulted in knowledge translation via new clinical treatment protocols. Our journey continues to further improve the specificity of childhood ALL therapy with goals of optimal efficacy and quality of life.
The Princess Máxima Center
In the Netherlands, nearly all childhood cancer research and clinical care are concentrated in a single institute, the Princess Máxima Center for Pediatric Oncology, in Utrecht. With approximately 600 children each year diagnosed with cancer in the Netherlands and 150 children suffering from relapse each year, our comprehensive center comprises the largest pediatric oncology institute in Europe. This provides a unique opportunity for the Netherlands to contribute to the world-wide effort in understanding and improving outcome for children with cancer.
