Gregory Friedman, MD

Over the past year, they completed a series of studies to determine the most promising vaccine targets and the safest and most effective way to deliver the vaccine, generating data that helped refine both the treatment strategy and clinical trial design. This work laid the scientific foundation for a first-in-children Phase 1 clinical trial of a next-generation oncolytic virus for newly diagnosed diffuse midline glioma, for which all regulatory approvals have now been secured. The trial is expected to open in early 2026 and will serve as the platform for incorporating the vaccine once initial safety is established, marking an important step in translating this work from the laboratory to patients.

Over the past six months, they have identified a safe way to deliver the vaccine directly into the brain and found that this method may be especially effective at reaching areas where tumors often spread, while also reducing side effects. Working with their industry partner, they are now developing an improved version of the vaccine to enhance safety. In addition, the team has completed the necessary steps to launch a new clinical trial using their next-generation virus therapy for children with diffuse midline glioma (DMG)-a deadly brain tumor with few treatment options. The trial is expected to launch in late 2025 and will serve as the foundation for future studies combining the virus and vaccine, bringing new hope to children facing these devastating brain cancers.

Collaborating with their industry partner, they have continued their search for the ideal protein target for use in their innovative vaccine technology. To this end, they have recently joined forces with a new collaborator to incorporate a novel antigen discovery platform into their cancer vaccine development. Additionally, they have evaluated three potential vaccine delivery methods and determined that intraventricular (IVT) delivery – administration directly into the brain’s ventricular system – may be the most effective at targeting brain tumors. In an effort to transition their work from bench to bedside, they have developed a clinical trial protocol to assess the safety and efficacy of the oncolytic virus as a standalone treatment in patients with newly diagnosed diffuse midline glioma. In parallel, they are working with their industry partner to design a trial that will evaluate the vaccine alone and combined with the virus in children with brain tumors. These efforts are a critical step forward in providing urgently needed, innovative therapies for children battling these difficult-to-treat brain tumors.

To achieve this goal, Dr. Friedman and his team are combining a cold-sore virus that has been modified to target and kill brain tumor cells, while not injuring normal brain cells, with a unique tumor vaccine designed to increase the immune attack on the tumor and increase tumor cell killing by the virus.

Support from CureSearch has enabled Dr. Friedman to assemble a “dream team” of researchers to develop this combination immunotherapy. Thus far, they have determined the ideal brain tumor proteins to target with the vaccine, and are developing a tumor model to specifically test those vaccines. Additionally, they have found that the combination therapy of the cold-sore virus with the novel tumor vaccine is more effective than either therapy alone and that the timing of the therapies is very important. They have shown that delivering the vaccine prior to the virus is more effective than giving the virus before the vaccine because it excites the immune system to attack the tumor instead of removing the virus, which allows the virus to kill more tumor cells. Dr. Friedman is continuing to study how this combination therapy works together and developing methods to test how well the therapy is working. Additionally, he is working with an industry partner to develop a clinical trial to test the safety and effectiveness of the vaccine alone and in combination with the virus in children with brain tumors who are in desperate need of new and improved therapies.

Working with their industry partner Vaccitech, Dr. Friedman has developed a flowchart for advancing to a clinical trial, and they are beginning to formulate a clinical protocol.

“Outcomes for children with high-grade gliomas including diffuse midline gliomas are unacceptably poor, and our standard therapies are minimally effective and toxic. We are thrilled to partner with CureSearch to help achieve our overall goal of developing safe and effective immunotherapies for pediatric high-grade gliomas. We have had early success using cold-sore virus G207 that kills tumor cells directly and stimulates the child’s immune system to attack the tumor.

This critical grant support from CureSearch enables us to assemble a “dream team” of researchers from academia including UAB and Children’s of Alabama, Dana-Farber, Cambridge, and Mount Sinai as well as industry partners Treovir (G207) and Vaccitech to develop a combination immunotherapy that can produce long-term responses with the virus and Vaccitech’s highly innovative SNAPvax tumor vaccine technology.

We plan to quickly translate the combination therapy to pediatric clinical trials with the goal of improving outcomes and lessening side effects for these children in desperate need of improved, targeted therapies.”