Medulloblastoma plasma membrane proteomics to inform optimal immunotherapy design

Brain cancer is the most common pediatric solid cancer, devastating the lives of more than 5,000 children and their families every year in North America. Current chemoradiotherapy approaches are often ineffective and cause serious side effects on the developing brain, such as permanent seizures and learning disabilities. Thus, more effective and less damaging therapies are urgently needed. Immunotherapy has been recently credentialed as a breakthrough in cancer therapy, with novel immunotherapy agents approved by the FDA for the treatment of childhood cancer. There is every indication that this progress presents the tip of the iceberg and that with continued efforts, effective immunotherapies can be developed for many currently incurable pediatric cancers. The ability for cancers to grow rapidly is in part due to the activation of specific proteins exposed on the membrane of cancer cells. The goal of immunotherapy is to target cells exposing these proteins while sparing normal, healthy cells; however, a major barrier is that most proteins on the surface of medulloblastoma cells are currently unknown. In this proposal we will identify optimal targets to ultimately develop immunotherapies against medulloblastoma.