Grant Awarded in 2024 following an in-depth review of high-quality funding applications by our world class Scientific Advisory Board.
Dr. Emmy Dolman from the Children’s Cancer Institute will study the potential for enhancing immunotherapy to treat neuroblastoma.
Unlocking Immune Escape: Enhancing Immunotherapy in High-Risk Neuroblastoma via Targeted AURKA Degradation
Immunotherapy has transformed cancer treatment for adults; however, children with high-risk neuroblastoma often do not benefit from these therapies.
This is because neuroblastoma creates a “cold” environment that avoids detection and elimination by the immune system, making it resistant to immunotherapy.
One key factor in this immune evasion is a gene called MYCN, which drives neuroblastoma and reduces the immune system’s ability to fight the cancer. However, MYCN is difficult to target directly with current treatments.
This research focuses on a protein called Aurora Kinase A (AURKA), which both stabilises MYCN and helps neuroblastoma to evade detection by the immune system. By using a new type of therapy called PROTACs (PROteolysis TArgeting Chimeras), Dr. Dolman and her team aim to degrade AURKA entirely, thereby disrupting the protein’s role in stabilising MYCN. This has the potential to make neuroblastoma more “visible” to the immune system and therefore sensitive to immunotherapy.
With this in mind, this project has two key goals:
- To investigate how AURKA degradation affects the immune environment of neuroblastoma.
- To develop a combination therapy using AURKA-targeting PROTACs and immunotherapy to enhance the effectiveness of treatment.
If successful, this project could lead to a groundbreaking combination treatment for high-risk neuroblastoma, and improve survival rates and quality of life for children facing this aggressive cancer.
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