Gregory Friedman, M.D., professor of pediatrics at the University of Alabama at Birmingham (UAB), director of developmental therapeutics for the Alabama Center for Childhood Cancer and Blood Disorders at UAB and Children’s of Alabama
It’s a pretty big deal when your research is published in the New England Journal of Medicine. But it’s just as rewarding when your research holds promise for treating one of the most deadly cancers seen in children: high-grade gliomas.
“Unfortunately, outcomes are very poor for children with progressive gliomas, and we have not seen a significant improvement in outcomes for this dreadful disease in the last 30 years,” said Gregory Friedman, M.D., professor of pediatrics at the University of Alabama at Birmingham (UAB), director of developmental therapeutics for the Alabama Center for Childhood Cancer and Blood Disorders at UAB and Children’s of Alabama and lead author of the paper, “Oncolytic HSV-1 G207 Immunovirotherapy for Pediatric High-Grade Gliomas.” Dr. Friedman also presented the findings from the phase 1 trial during the virtual American Association for Cancer Research Annual Meeting in April 2021.
“The toxicities associated with the current standard therapies are unacceptably high,” Dr. Friedman said. “There is, therefore, a great need for effective and less toxic targeted therapies for these children.”
Dr. Friedman’s team used a genetically engineered cold-sore virus, a herpes simplex virus type-1 (HSV-1), which naturally infects cells of the peripheral and central nervous system. While the modified virus, called “G207,” can’t infect and harm normal cells, it can target tumor cells by directly killing the cells and stimulating the child’s own immune system to attack the tumor.
Twelve patients between 7 and 18 years old with high-grade gliomas that had progressed on prior treatments received an infusion of G207 through intratumor catheters. Within 24 hours, some also received a single, small radiation dose directed to their tumors, which was designed to enhance virus replication and spread throughout the tumor.
Treatment response was assessed by imaging, tumor pathology and the patient’s performance status. Eleven of the 12 patients demonstrated a response, with a median overall survival of 12.2 months; a 120 percent increase over the typical overall survival of 5.6 months in this population. To date, 36 percent of patients have survived longer than 18 months, surpassing the median overall survival for newly diagnosed pediatric high-grade glioma.
To date, immunotherapies have failed to improve outcomes in pediatric brain tumors because the tumors are “cold,” with very few immune cells needed to attack the tumor, Dr. Friedman said. “Importantly, when examining matched pre- and post-treatment tissue from patients, we showed something that has not been seen before with any other therapy: that G207 dramatically increased immune cell trafficking to the tumors and turned the ‘cold’ tumors to ‘hot’ ones. This is a critical step in the development of an effective immunotherapy for children with brain tumors,” he said.
G207 alone or in combination with radiation therapy was well tolerated, with no dose-limiting toxicities, grade 3/4 treatment-related adverse events, or evidence of virus shedding into the bloodstream, saliva, or conjunctiva.
“While further investigation in a phase 2 clinical trial is needed, our findings suggest that oncolytic immunovirotherapy using a modified cold-sore virus is a safe and potentially efficacious approach to target pediatric high-grade glioma,” Dr. Friedman said.
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