Gregory Friedman, MD

MD Anderson Cancer Center

in collaboration with Avidea Technologies, Dana-Farber Cancer Institute, Broad Institute of MIT and Harvard, Harvard Medical School, Brigham and Women’s and Boston Children’s Hospital, University of Cambridge, Northwestern University, Lurie Children’s Hospital and Treovir, LLC

CureSearch Acceleration Initiative Award: 2022-2025

Focus: Pediatric High-Grade Glioma

Project title: Overcoming the Adverse Microenvironment of Pediatric High-Grade Gliomas

Gregory Friedman, MD, specializes in pediatric neuro-oncology and conducting pediatric brain tumor research as Professor of Pediatrics and Section-Chief of Pediatric Neuro-Oncology at the University Texas MD Anderson Cancer Center. He previously served as Director of Developmental Therapeutics for the Alabama Center for Childhood Cancer & Blood Disorders at the University of Alabama at Birmingham and as the site PI for the Children’s Oncology Group Pediatric Early Phase-Clinical Trial Network (PEP-CTN). His overarching goal is to improve outcomes for children with brain tumors by developing and improving novel, targeted immunotherapies in the lab and then translating these therapies to clinical trials. His research is focused on determining mechanisms of cancer cell therapeutic resistance to novel therapeutics by exploring the role of the tumor microenvironment and cellular defense mechanisms to circumvent resistance mechanisms.

His experience in managing pediatric neuro-oncology patients and in conducting clinical oncology research complements his laboratory experience, which has enabled his team to develop a greater understanding of the tumor microenvironment and translate innovative immunotherapies from bench-to-bedside. He was the PI for the first completed oncolytic virotherapy (G207) pediatric brain tumor trial (NCT02457845; published in New England Journal of Medicine in 2021), and he is the PI for an ongoing first-in-human trial of G207 in recurrent cerebellar tumors (NCT03911388). In addition, he developed and leads a Phase 2 trial of G207 through the NCI-supported Pediatric Brain Tumor Consortium in recurrent pediatric high-grade glioma.

"The overarching goal of this CureSearch application is to overcome the cold, unfavorable tumor microenvironment of pediatric high-grade gliomas and diffuse midline gliomas by combining G207 with Avidea’s SNAPvax (self-assembling nanoparticle TLR-7/8 peptide tumor vaccine). Our preliminary data indicates that the combination is superior to either therapy alone. We will develop this combination and translate the approach from bench-to-beside through our collaborations with leading investigators across the globe and our public-private partnerships with biotechnology companies Treovir and Avidea Technologies. We have the experience and expertise to accomplish the proposed aims, and we have demonstrated the required experience in bench-to-bedside translation of novel therapeutics. We are positioned to rapidly translate the approach to clinical trials to positively impact children who are in desperate need of novel, targeted therapies." - Dr. Gregory Friedman, MD

Collaborative Team

Through the critical grant support from CureSearch, he has assembled a “dream team” of researchers from academia including MD Anderson Cancer Center, Dana-Farber, Cambridge and Mount Sinai as well as industry partners Treovir and Barinthus to develop a novel immunotherapy combining oncolytic virotherapy and an innovative vaccine technology. The overarching goal of the research is to quickly translate the combination therapy to pediatric clinical trials with the aim of improving outcomes and lessening side effects for children with brain cancer in desperate need of improved, targeted therapies.

Outcomes for pediatric high-grade gliomas (pHGGs) range from less than 25% to essentially 0%, in the case of diffuse midline gliomas (DMGs), and these dismal survival rates have not improved in 30 years. Safe, effective immunotherapies for pediatric high-grade glioma (pHGG) including diffuse midline glioma (DMG) have eluded investigators and represent a significant unmet need.

Gregory Friedman, MD, is a CureSearch Acceleration Initiative Award recipient conducting research at the MD Anderson Cancer Center. He and his colleagues are currently conducting a phase I clinical trial in pediatric high-grade glioma and have demonstrated that their oncolytic virus, G207, is safe with very promising efficacy. An oncolytic virus is a virus that is specifically able to enter and destroy cancer cells. Based on the results of the phase I trial, G207 was awarded FDA Fast Track Designation, and Dr. Friedman is developing a multi-institutional Phase 2 trial. While he continues to advance G207 clinically, Dr. Friedman’s goal is to maximize G207’s therapeutic benefit for future clinical trials. In this project, Dr. Friedman will be assessing a combination immunotherapy that he and his colleagues hypothesize will result in a stronger and sustained response to G207 resulting in lasting anti-tumor response. Dr. Freidman will assess combination of G207 with a highly innovative vaccine platform developed by his public-private collaborating partner, Avidea Technologies. In initial proof-of-principle preclinical mouse studies, vaccination prior to G207 treatment significantly enhanced efficacy compared to either therapy alone. The goal of this AI award will be to develop a protocol and obtain regulatory approvals for a Phase 1 clinical trial of the Avidea vaccine (SNAPvax) and G207.

Thank you, Rally Foundation for Childhood Cancer Research and LifeArc for supporting this innovative project.

Research Update December 2024:

Dr. Friedman and his team have made remarkable progress in advancing a novel combination immunotherapy for children with brain tumors. 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.

Research Update April 2024:

The goal of Dr. Friedman’s project is to develop a treatment for brain tumors that helps a child’s own immune system directly attack tumor cells while avoiding damage to normal cells in the body to improve outcomes. 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.

Research Update December 2023:

The team has identified additional antigens to target and is developing those vaccines. 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."

- Dr. Gregory Friedman

Gregory Friedman, MD – Acceleration Initiative – Pediatric High-Grade Gliomas