Neuroblastoma is a cancer of the nervous system that occurs in young children and is often lethal. An improved understanding of neuroblastoma tumorigenesis is urgently needed to catalyze development of innovative and effective therapies. Recent immunotherapy advances have provided optimism for the use of this treatment type in children with neuroblastoma. However, there is a desperate need for new molecules that can be safely and specifically targeted with immune-based therapeutic approaches. Recent work showed that a protein called glypican-2 (GPC2) is abundant on neuroblastoma cells, but not found on normal cells, and that GPC2 helps neuroblastomas grow aggressively. Thus, GPC2 may be an ideal cell surface molecule to target with immune-based therapies. Dr. Bosse seeks to validate GPC2 as a candidate for engineered targeted immune cells in high-risk neuroblastoma. This research will also define how GPC2 promotes cancer growth, thus providing additional critical knowledge for the therapeutic exploitation of an important tumor-sustaining pathway. Finally, this work will help establish a robust pipeline for the identification of novel tumor-specific molecules for immunotherapeutic targeting in pediatric cancer. This blueprint will allow for the rapid translation of prioritized molecules to a clinically available targeted immunotherapeutic, with an aim to make meaningful differences in the clinical care of children with high-risk pediatric malignancies.