Oncolytic virus therapy for malignant gliomas: entering the new era

ABSTRACT

Introduction

To overcome the challenge of treating malignant brain tumors, oncolytic viruses (OVs) represent an innovative therapeutic approach, featuring unique mechanisms of action. The recent conditional approval of the oncolytic herpes simplex virus G47Δ as a therapeutic for malignant brain tumors marked a significant milestone in the long history of OV development in neuro-oncology.

Areas covered

This review summarizes the results of recently completed and active clinical studies that investigate the safety and efficacy of different OV types in patients with malignant gliomas. The changing landscape of the OV trial design includes expansion of subjects to newly diagnosed tumors and pediatric populations. A variety of delivery methods and new routes of administration are vigorously tested to optimize tumor infection and overall efficacy. New therapeutic strategies such as combination with immunotherapies are proposed that take advantage of the characteristics of OV therapy as an immunotherapy. Preclinical studies of OV have been active and aim to translate new OV strategies to the clinic.

Expert opinion

For the next decade, clinical trials and preclinical and translational research will continue to drive the development of innovative OV treatments for malignant gliomas and benefit patients and define new OV biomarkers.

KEYWORDS:

• Brain tumor
• clinical trial
• glioma
• immunotherapy
• oncolytic virus therapy
• preclinical study
• tumor microenvironment

Article highlights

• Malignant gliomas remain a deadly tumor type and innovative therapeutic strategies are needed.

• The recent approval of G47Δ for the treatment of malignant gliomas in Japan represents a significant milestone in the long history of clinical development of oncolytic viruses (OVs) as brain tumor therapeutics.

• Currently, seven different OV platforms including both DNA and RNA viruses are actively being investigated in phase I and II trials for glioma patients.

• OV clinical trials began to expand the study subjects to newly diagnosed tumors and pediatric patients, driving search for populations and disease state that most likely benefit from OV therapy.

• Extensive clinical and preclinical research is underway to optimize the delivery of OVs, testing a variety of delivery methods and routes of administration.

• Rationally designed OV immunotherapy strategies continue to drive the field as researchers generate new armed OVs and combine OVs with other immunotherapies to overcome the suppressive tumor immune microenvironment.

• Concerted efforts by laboratory and clinical investigators will advance the field, increase our understanding of mechanisms of action and biomarkers of OV as well as clinically benefit patients with glioma in the next decade.

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Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

A reviewer on this manuscript has disclosed that they are on the advisory board for Oncorus, Inc. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Additional information

Funding

H Fudaba is supported by the Uehara Memorial Foundation.