The research within our LUMC departments is conducted within departmental research programmes. The research programme below is embedded within the department of Pediatrics.
Aim and focus
Pediatric research program 31301 encompasses research on the immunological aspects of allogeneic stem cell transplantation (SCT) in malignant and non-malignant diseases as well as tumor immunology in bone tumors, Juvenile Idiopathic Arthritis (JIA), Celiac Disease (CD) and Langerhans Cell Histiocytosis (LCH). The common denominator of these well-established research projects is to identify molecular mechanisms of disease and to develop novel therapeutic and/or preventive strategies to modulate these immune-mediated diseases leading to improvement of health care and quality of life of pediatric patients.
Position in international context
The pediatric SCT unit is one of the most prominent facilities in Europe with a frontline translational research program, including many multicenter/-national studies. The research lines on JIA, CD and LCH also belong to the frontiers of research in their areas. The SCT program is represented in the scientific boards of several international SCT organizations (EBMT and I-BFM). Both the SCT and CD program have coordinated EU funded projects.
Content / highlights / achievements
- Clinical, multicenter protocols using adoptive transfer of mesenchymal stromal cells for improved stem cell engraftment and the treatment of steroid-refractory acute graft-versus-host disease, including the role of indicative biomarkers, have been successfully explored.
- Implementation of adenovirus-specific T cell therapy in pediatric SCT patients
- Immuno-pharmacological studies on antibody therapy in the SCT setting have revealed large inter-individual differences correlating with clinical outcome, and provide a rationale for implementation personalized treatment.
- Antitumor activity of activated NK cells and macrophages against bone tumors and molecular mechanisms involved have been demonstrated in preclinical studies.
- Preclinical studies on anti-tumor activity of NK cells in pediatric cancer have been translated into a clinical trial with activated NK cells after SCT in pediatric leukemia.
- In patients with JIA genetic associations with susceptibility to and severity of disease have been discovered in multicenter studies.
- Characterization of the host immune response and tumor genetics have resulted in increased knowledge of the pathophysiology and clinical behavior of LCH.
- Guidelines for the diagnosis of CD in children have been developed in international collaboration. In a collaborative EU funded international study the possibilities to induce tolerance for gluten in young children with high risk for CD is explored.
- The common theme within this research line will be to translate the knowledge obtained into the development of personalized treatment regimens in SCT recipients as well as patient care in juvenile arthritis and celiac disease. This should lead to improvement in clinical outcome and minimization of treatment related adverse events. Research will be focused on: SCT/immunotherapy
- Improvement of SCT regimens for malignant and non-malignant diseases leading to better engraftment of hematopoietic stem cells, tolerance induction, and immune reconstitution, including antitumor reactivity, after SCT
- Clinical implementation of gene therapy for inborn immunodeficiency and related disorders. Juvenile idiopathic arthritis
- Define genetic variants related to the clinical course of disease with the aim to identify novel targets for therapeutic intervention and tools for prediction of the course of disease. Celiac disease
- Translating results of basic science in prevention, diagnosis and treatment of CD by inducing of tolerance to gluten and by application of mobile-health systems.
Cohesion within LUMC
The research program fits in the medical research profiles “Immunity, Infection and Tolerance” and “Cancer Pathogenesis and Therapy” of the LUMC.Collaborations are ongoing with the departments of: Pathology (LCH), Molecular Cell Biology and Medical Microbiology (host-pathogen interactions), Gastroentrology (CD, IBD) Hematology (virus- and tumor-specific T cell therapies), Immunohaematology and Blood Transfusion (mesenchymal stromal cells, NK cells, alloimmune T-cells and microchimerism, CD and gene therapy), Rheumatology (JIA), Neurology (autoimmune disease of the neuromuscular synaps), Clinical Pharmacology and Toxicology (pharmacokinetics) and Medical Statistics (genetic association studies). The CD program is part of the LUMC Biobanking.