Validating GPC2 as an Immunotherapeutic Target in Medulloblastoma
Medulloblastoma is a cancer that occurs in young children and is often lethal. Recent immunotherapy advances have resulted in enthusiasm for the use of this treatment in children with pediatric cancers. However, we desperately need new molecules to safely and specifically target medulloblastomas with immunotherapy. Ideal immunotherapeutic targets should be located on the surface of tumor cells, expressed robustly on tumor cells but not on normal tissues and play a role in helping tumors grow. We have discovered that a protein called GPC2 meets these criteria in several pediatric cancers including neuroblastoma and medulloblastoma. We have developed a new immunotherapy, a GPC2-targeting antibody-drug conjugate (ADC), which safely delivers a potent drug to tumor cells by binding to GPC2 on the tumor cell's surface, internalizing into the cell and inducing damage to the tumor cell's DNA thus causing cell death. We have shown that this ADC immunotherapy is effective in treating neuroblastoma cells and are now interested in extending this potent therapeutic to other cancers. Preliminary studies have shown that GPC2 is robustly expressed in medulloblastoma cells and potentially on the cell surface, but it remains unclear if the GPC2 ADC we developed will be equally as potent in treating medulloblastoma cells.
This project will first focus on validating GPC2 cell surface expression on medulloblastoma preclinical models and ensuring the GPC2 ADC can be internalized into medulloblastoma cells. We will next test the efficacy of this GPC2 ADC in medulloblastoma preclinical models. Thus, this work will possibly directly lead to a new therapy that will improve outcomes for children with medulloblastoma and potentially other GPC2-expressing pediatric tumors.
Mentored by Dr. Kristopher Bosse
Children’s Hospital of Philadelphia, Philadelphia, PA