Investigating DLL3 as a Candidate Immunotherapeutic Target in Neuroblastoma
Background
Neuroblastoma is an extra-cranial pediatric malignancy that arises from aberrant neuronal development. Neuroblastoma is the most common cancer in children less than a year old and despite currents therapies, survival rates for children with this high-risk disease are poor. Therefore, we need to develop effective treatment strategies for these neuroblastoma patients. Current cancer research has focused on immunotherapeutic approaches, one of which involves identifying cell-surface molecules that are expressed exclusively on tumor cells in order to selectively deliver a chemotherapy agent. Due to the developmental nature of neuroblastoma, these cells express unique cell-surface molecules that are not expressed in mature cells. Additionally, cancer cells could be dependent on these cell-surface molecules for survival, which may make these malignancies susceptible to immunotherapy.
Project Goal
The Maris lab has identified cell-surface proteins that are highly expressed on neuroblastoma cells. One such candidate is delta-like 3 (DLL3), which is known to inhibit a canonical cell signaling pathway. DLL3 has also been investigated as an immunotherapeutic target in other cancers, including neuroendocrine and small cell lung cancers and an antibody-drug conjugate targeting DLL3 has shown efficacy in a phase 1 clinical trial. However, it is unclear whether or not DLL3 is an oncoprotein critical to neuroblastoma tumorigenesis or if DLL3 would be a useful immunotherapeutic target in neuroblastoma. We will investigate the role of DLL3 in neuroblastoma cell survival and understand the signaling pathways associated with DLL3 expression.
Mentored by Dr. John Maris
Children’s Hospital of Philadelphia, Philadelphia, PA
