Patrick Y. Wen, MD
“This study is interesting, and the results were a little surprising,” said Patrick Y. Wen, MD, Professor of Neurology at Harvard Medical School and Director of the Center for Neuro-Oncology at Dana-Farber Cancer Institute.
“The prognosis of these tumors in children and adolescents is so terrible that anything that has a suggestion of efficacy is, of course, of interest,” Dr. Wen said, responding to a question about why this study of 11 children was selected for publication in The New England Journal of Medicine. He was cautiously optimistic about the robust results of the study: “This is only a small number of patients, and there could be a selection bias.”
Less Efficacy in Adults
“The G207 oncolytic herpes virus was tested in adults with gliomas with much less efficacy,” Dr. Wen continued.
Dr. Wen suggested several explanations for the poorer showing in adults. “The preclinical models suggested that pediatric tumors were more sensitive to G207. Children have much lower levels of neutralizing antibodies than adults. In the study, children without antibodies had a better response. In the adult study, the tumor was resected, and the virus was injected into the wall of the cavity. In this study, they infused the virus over 6 hours, potentially allowing the virus to extend into the surrounding tissue and parenchyma to a much greater extent,” he continued.
“There is still a lot of interest in herpesvirus in adults, and several studies with different herpesviruses are ongoing,” he added.
Future Directions for High-Grade Glioma Treatment
Noting the growing interest in viruses to treat gliomas, Dr. Wen commented: “In addition to viruses growing within the gliomas and killing the cancer cells, they can induce an inflammatory response and convert ‘cold’ tumors into ‘hot’ tumors. We are not sure if the T cells seen in the tumors in this study were directed at viral or tumor antigens or a general inflammatory response.”
Another “hot” area for a different type of high-grade glioma—a brain stem tumor called diffuse intrinsic pontine glioma—is the use of chimeric antigen receptor (CAR) T-cell therapies. Currently, a phase I study of GD2 CAR T-cell therapy is being conducted at Stanford, he noted.
DISCLOSURE: Dr. Wen has served in a consulting or advisory role for Agios, Astra Zeneca, Bayer, Black Diamond, Boston Pharmaceuticals, Chimerix, CNS Pharmaceuticals, Elevate Bio Immunomic Therapeutics, Imvax, Karyopharm, Merck, Novartis, Nuvation Bio, Vascular Biogenics, VBI Vaccines, Voyager, QED, Celularity, and Sapience; and has received institutional research funding from Agios, Astra Zeneca/Medimmune, Beigene, Celgene, Eli Lily, Genentech/Roche, Kazia, MediciNova, Merck, Novartis, Nuvation Bio, Oncoceutics, Vascular Biogenics, and VBI Vaccines.
Treatment with genetically engineered oncolytic herpes simplex virus type 1 (HSV-1) G207 alone or with radiation resulted in encouraging outcomes in a small study of pediatric patients with high-grade glioma. In a phase I trial, responses were observed in 11 of 12 children, and median overall...