Research Perspectives:
Intraventricular immunovirotherapy; a translational step forward
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Abstract
Joshua D. Bernstock1,2,*, Sarah Blitz1,*, Kyung-Don Kang3 and Gregory K. Friedman3
1 Department of Neurosurgery, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA
2 David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
3 Department of Pediatrics, Division of Pediatric Hematology and Oncology, University of Alabama at Birmingham, Birmingham, AL 35233, USA
* These authors contributed equally to this work
Correspondence to:
Joshua D. Bernstock, | email: | [email protected] |
Gregory K. Friedman, | email: | [email protected] |
Keywords: oncolytic virotherapy; herpes simplex virus (HSV); G207; intraventricular therapy; leptomeningeal disease
Received: December 19, 2022 Accepted: December 23, 2022 Published: January 12, 2023
ABSTRACT
Oncolytic virotherapy with intratumoral engineered type-1 herpes simplex virus (HSV) has been proven safe with promising efficacy in recent clinical trials for treatment of both pediatric and adult high-grade glioma. However, this approach excludes patients with tumors in surgically inaccessible and/or eloquent brain regions. Current delivery methods are also unable to access/treat those patients with metastatic disease in the spinal cord and/or leptomeningeal disease. A recent preclinical study has paved the way for clinical translation of intraventricular administration of oHSV by identifying and mitigating the toxicity associated with this route for therapeutic benefit in murine models of disseminated medulloblastoma. This work may ultimately allow for targeting of intractable disease and provides a feasible option for the repetitive dosing of clinically relevant immunovirotherapy, G207.
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