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Oncolytic HSV-1 G207 Immunovirotherapy for Pediatric High-Grade Gliomas
Gregory K Friedman1, James M Johnston1, Asim K Bag1
1From the Department of Pediatrics, Divisions of Pediatric Hematology-Oncology (G.K.F., K.K., L.N., K.-D.K., S.T., C.S., A.M.-S.), Pediatric Allergy and Immunology (T.P.A.), and Pediatric Infectious Disease (R.J.W.), and the Departments of Neurosurgery (G.K.F., J.M.J., J.M.M., G.Y.G.), Pathology (R.L.), Biostatistics (I.A.), and Radiation Oncology (J.B.F.), University of Alabama at Birmingham, and Children's of Alabama (G.K.F., J.M.J., R.L., K.K., A.M.-S., T.P.A., R.J.W.) - both in Birmingham; the Department of Diagnostic Imaging, St. Jude Children's Research Hospital, Memphis (A.K.B.), and the Department of Pediatrics, Vanderbilt University Medical Center, Nashville (D.P.) - both in Tennessee; the Department of Neurosurgery, Brigham and Women's Hospital and Boston Children's Hospital, Harvard Medical School, Boston (J.D.B.); the Department of Pediatrics, Albert Einstein College of Medicine (A.M.M.), and the Departments of Pediatrics (S.F.S., Y.K., M.A.K.) and Neurology (Y.K.), Memorial Sloan Kettering Cancer Center - both in New York; the Department of Pediatrics, University of Oklahoma Health Sciences Center, Oklahoma City (R.M.-K.); the Division of Pediatric Hematology, Oncology, and Bone Marrow Transplant (K.W., D.S.O., M.S.A.) and the Department of Pediatric Neurosurgery (J.L.), Nationwide Children's Hospital, and the Department of Radiation Oncology, Ohio State University Comprehensive Cancer Center (J.D.P.) - both in Columbus; and the Division of Pediatric Hematology, Oncology, and Bone Marrow Transplant, Washington University School of Medicine, St. Louis (M.S.A.).
Oncolytic virus G207 showed promising results in a phase 1 trial for pediatric high-grade glioma, improving survival and converting "cold" tumors to "hot" by increasing tumor-infiltrating lymphocytes.
Area of Science:
- Neuro-oncology
- Virology
- Immunology
Background:
- Pediatric high-grade gliomas (HGG) have poor prognoses with a median survival of 5.6 months.
- These tumors are typically immunologically
- cold,
- exhibiting limited tumor-infiltrating lymphocytes.
- Genetically engineered herpes simplex virus type 1 (HSV-1) G207 is a promising oncolytic virus preclinically.
Purpose of the Study:
- To evaluate the safety and preliminary efficacy of intratumoral G207 in children and adolescents with recurrent or progressive high-grade glioma.
- To assess the immunologic effects of G207 on tumor microenvironment.
Main Methods:
- A phase 1, 3+3 dose-escalation trial involving four cohorts of pediatric patients with supratentorial brain tumors.
- Stereotactic placement of intratumoral catheters for G207 infusion (10^7 or 10^8 PFU).
- Radiation therapy (5 Gy) was administered to cohorts 3 and 4 post-G207; viral shedding and tumor-infiltrating lymphocytes were monitored.
Main Results:
- Twelve patients (7-18 years) with high-grade glioma received G207; no dose-limiting toxicities were observed.
- Eleven patients showed radiographic, neuropathological, or clinical responses.
- Median overall survival was 12.2 months, with 4 of 11 patients alive at 18 months; G207 increased tumor-infiltrating lymphocytes.
Conclusions:
- Intratumoral G207, alone or with radiation, demonstrated an acceptable safety profile in pediatric high-grade glioma.
- G207 treatment converted immunologically "cold" tumors into "hot" tumors, suggesting potential for enhanced anti-tumor immunity.
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