Prof. Geert van den Bogaart from the Groningen Biomolecular Sciences and Biotechnology Institute (GBB) is a partner in a ZonMw Open project, which has received a grant of EUR 680,000. The grant is for the project ‘Optimizing the design of dendritic cell vaccine immunotherapies’. Other partners are researchers from Radboud University and Leiden University. Prof. Van den Bogaart will receive EUR 200,000 for his part in the research project. He will focus on how the chemical modifications of peptide vaccines affect the cellular mechanisms of T cell activation.
Dendritic cell immunotherapy is a new breakthrough in cancer treatment. In this treatment, dendritic cells (DCs) are first isolated from the blood of melanoma patients. These DCs are then loaded with cancer-specific peptides and returned to the patient. Here the DCs present the cancer-specific peptides to so-called killer T cells. This activates the cancer-recognizing killer T cells, which can then destroy the cancer cells.
Interim results from a large-scale clinical trial at Radboudumc Nijmegen show that dendritic cell vaccines only seem to work in a relatively small group of patients. Preclinical data from the research consortium and several published scientific studies show that the efficiency of killer T cell activation can be increased enormously (several orders of magnitude) by relatively small chemical modifications of the peptides. The exact cellular mechanism of how this occurs and how it is affected by the chemical modifications are unknown. Examples of chemical modifications that can enhance anti-cancer T cell activation include extending the peptides, altering their chemical-physical properties, and linking to ligands for specific uptake receptors. Based on these results, the researchers believe that chemical changes can significantly improve DC therapies. Most likely, due to simple and clinically permissible chemical changes to the peptides used, they can dramatically increase clinical effectiveness in curing melanoma.
The aim of the ZonMw Open Competition is to create space for excellent, curiosity-driven, groundbreaking science. The grant offers excellent research groups the opportunity to renew their line of research, enter into new collaborations and perform studies of exceptional quality in the field of health.
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