The goal of this project is to develop intraventricular delivery of oncolytic HSV and to augment Dr. Friedman's training and education. The critical first step in developing this potential therapy is determining the cause of toxicity. In the first year, we determined that only active virus and not inactivated virus or vehicle caused toxicity, and virus was seen in the ependyma. We established the timing of the inflammatory response post-injection of the virus with a peak response seen at day 4 and a decline seen by day 7. The ependymal lining regenerated over several weeks although not completely. When the virus dose was decreased by a log, toxicity was reduced and the virus prolonged survival and decreased metastases in a pediatric medulloblastoma model. Overall, these findings will expand scientific knowledge in the fields of virotherapy and immunotherapy, and will have an impact on the development of future viral vectors and potentially future clinical trials. Lastly, the first year of this career development award has contributed greatly to Dr. Friedman's training and educational development in pediatric brain cancer research.