Oncolytic Virus to Potentiate Immune-checkpoint Blockade in Immunologically Cold Pediatric Brain Tumors

Some common viruses (e.g. measles, poliovirus) preferentially infect and kill tumor cells. This fact was discovered at the beginning of the 20th century. However, it was not until recently that this approach was recognized as an immunotherapy. It has been shown that viruses have the ability to stimulate an immune response in solid tumors with an otherwise inactive or “cold” immune system. This method is referred to as the use of oncolytic virus. The project will explore the use of oncolytic viruses through the analysis of tumor biopsies. This project is partially based on specimens from an ongoing clinical trial (NCT02962167) for measles virus in pediatric medulloblastoma. The Children’s Brain Tumor Network has carefully archived these tissues and this work is only possible as a result of those efforts. The ongoing Phase I trial supports the strategy of combination therapy and the use of oncolytic viruses in this combination. Thus, therapy combinations developed in this project will form the basis of an expansion of this trial and better outcomes for medulloblastoma patients as a result.