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Jan Molenaar / Judith Wienke

12. A game of hide and seek: targeting neuroblastoma’s escape from immunotherapy

Our group aims to translate immunological and molecular genetic knowledge of pediatric solid tumors into new therapeutic interventions, with a specific focus on neuroblastoma. We combine different areas of expertise and state-of-the-art techniques including single-cell RNA-sequencing and high-dimensional flow cytometry of the tumor immune environment, high-throughput drug screening, precision medicine, and bioinformatics to identify novel (combination) therapies.

This highly translational project specifically addresses the clinical problem that in ca 50% of patients, neuroblastoma tumors evade the current immunotherapy with anti-GD2. Most of these patients don’t survive, and currently we cannot predict which patients will respond to anti-GD2. This project will focus on identifying treatments that can either undermine tumor immune evasion or increase the anti-tumor activity of immune cells.

You will use advanced techniques including high-throughput drug screening and CRISPR screening of neuroblastoma for anti-GD2 resistance to identify novel combination strategies. Moreover, you will have access to primary tumor fragments to study the effect of ex vivo anti-GD2 treatment on activation and remodeling of the tumor immune environment, and to explore whether these ex vivo responses can predict clinical responses in patients. The identified promising combination strategies will be validated in vitro and in vivo using our available neuroblastoma models (e.g. organoids, mouse models) with the goal of translating them into the clinical setting. Lastly, part of this project will be a data-oriented systematic literature review (called target actionability review) of candidate immunotherapy targets with the highest potential for clinical translation.

Necessary skills for this position:

  • Master’s degree in Medical Biology, Computational Biology, Life Sciences or related field
  • Previous experience with both ‘dry’ lab (data analysis) and ‘wet’ lab (cell culture, flow cytometry) is a appreciated
  • Expertise in (tumor) immunology and immunological techniques is preferred

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