Game Changer Grant Awarded to David Ashley

The purpose of this research project is to prepare a new form of immunotherapy for brainstem tumors in children for clinical trials. Cancer immunotherapy aims to enable a patients’ own
immune system to fight the cancer. Our approach is based on a safe, genetically engineered version of poliovirus, called PVSRIPO. PVSRIPO has demonstrated promise in clinical trials
against the most aggressive brain tumor in adults, glioblastoma. In May of 2016, the Food and Drug Administration granted Breakthrough Therapy Status to PVSRIPO.

In the current PVSRIPO trial, the virus is injected directly into the brain tumor. Because this is not possible in brainstem tumors, due to their very sensitive location, we adapted our strategy to make
it useful in new ways. We can alter the virus in the lab, so it will stimulate an immune response specifically against a mutation that is common in children’s brainstem tumors. With this strategy,
treatment occurs by standard injection into a muscle, similar to common vaccines such as the tetanus vaccine.

One of the biggest challenges in cancer immunotherapy is to raise the type of immune response that is strong enough to fight the tumor. Enlisting viruses in this fight is particularly attractive, because our immune system is naturally specialized to respond to virus infection. Therefore, PVSRIPO can engage the immune system in ways that no other form of therapy can. The research in this proposal will provide the evidence needed for obtaining permission from the Food and Drug Administration to start clinical trials in children with brainstem tumors.