A modified herpes virus, alone and in combination with radiation, has been shown to be well tolerated and effective in children with high-grade brain tumors – or gliomas – researchers at the University of Alabama at Birmingham and Children’s of Alabama have found.
The findings were presented at the Virtual American Association for Cancer Research Annual Meeting 2021 April 10-15 and published online in the New England Journal of Medicine.
Brain tumors are the most common solid tumor in children, and aggressive types such as glioblastoma have an extremely low survival rate, only 10% five years after diagnosis. Even tumors successfully treated by surgery, radiation and chemotherapy have a high recurrence rate.
“This is the first study to use a viral immunotherapy directly into the tumor of children with brain tumors, and the results indicate that the engineered herpes virus can be safely delivered into tumors located in all parts of the cerebrum in children. said Dr. Gregory Friedman, professor in the department of pediatrics at UAB who is a research scientist at UAB O’Neal Comprehensive Cancer Center and director of developmental therapies for the Alabama Center for Childhood Cancer and Blood Disorders at UAB and Children’s of Alabama. “The main findings so far are that the approach is safe and well-tolerated, and preliminary evidence of efficacy is promising.”
In the phase 1 clinical trial involving 12 patients between the ages of 7 and 18, the researchers used a modified virus known as G207, derived from the herpes virus responsible for cold sores. The virus has been genetically altered so that it only infects tumor cells. When the virus is injected into a malignant brain tumor through a catheter, it invades the tumor cells and replicates. This kills the cell and frees the offspring of the virus to hunt other tumor cells. In addition, the virus elicits a strong response from the body’s immune system, which can attack the tumor. The trial tested G207 alone and then combined with a single low dose of radiation to increase virus replication and spread through the tumor.
G207 is the product of more than 30 years of research. Dr. James Markert, who chairs the UAB Neurosurgery Department, was part of the Massachusetts General Hospital team that developed the concept of using oncolytic herpes viruses in the early 1990s. He worked on the parent virus for G207 and conducted the first clinical study of G207 at UAB. Today, the use of viral therapies for almost every type of cancer is being explored.
A second-generation virus, called M032, has been developed by Markert and associates Yancey Gillespie, professor of neurosurgery, and Dr. Richard Whitley, professor of pediatric infectious diseases, and is in clinical trials on UAB in adults with glioblastoma. UAB researcher Dr. Renee Chambers uses M032 in a study of brain tumors in dogs, which can develop tumors very similar to those in humans.
In the current study with G207, 11 out of 12 patients responded to treatment. The overall survival rate was more than double the typical rate for children with high-grade glioma. Approximately 36% of patients have survived more than 18 months to date, exceeding the medial overall survival for newly diagnosed patients with high-grade glioma.
Friedman’s team reports that G207 alone or in combination with radiation therapy was well tolerated, with no serious side effects attributed to the treatment.
“More studies are needed; but so far, viral immunotherapy with several viruses, including the herpes virus, has shown promising results for the treatment of high-quality brain tumors in both adults and children, ”said Friedman. “We also have an ongoing clinical trial to test the safety of G207 when administered into the cerebellum, an area of the brain that has not been previously tested in adults or children, but is the most common site for its onset. Of pediatric tumors. “
Friedman said the next steps are to determine the ideal timing to treat patients and what therapies can be used with viral immunotherapy to maximize the anti-tumor immune response. Based on the encouraging Phase 1 results, he and his team are working with the Pediatric Brain Tumor Consortium to develop a multi-institutional Phase 2 study of G207 for progressive pediatric high-grade glioma, which they hope to initiate this year.
The study was supported by the Food and Drug Administration’s Orphan Products Clinical Trials Grants Program, Cannonball Kids’ Cancer Foundation, the Rally Foundation for Childhood Cancer Research, Hyundai Hope on Wheels, St. Baldrick’s Foundation and the Kaul Pediatric Research Institute. G207 was supplied by Treovir LLC.
Friedman is backed in part by contracts between UAB and Eli Lilly and Co. and Pfizer. Markert and Whitley have financial interests in Treovir. They were not involved in any aspect of the conduct or data analysis of the study.
This story originally appeared on the UAB News website.
(Courtesy of Alabama NewsCenter)