Preprint Review Version 1 Preserved in Portico This version is not peer-reviewed

Oncolytic Viruses for Malignant Glioma: On the Verge of Success?

Version 1 : Received: 30 April 2021 / Approved: 3 May 2021 / Online: 3 May 2021 (11:01:14 CEST)

How to cite: Suryawanshi, Y.R.; Schulze, A.J. Oncolytic Viruses for Malignant Glioma: On the Verge of Success?. Preprints 2021, 2021050007 (doi: 10.20944/preprints202105.0007.v1). Suryawanshi, Y.R.; Schulze, A.J. Oncolytic Viruses for Malignant Glioma: On the Verge of Success?. Preprints 2021, 2021050007 (doi: 10.20944/preprints202105.0007.v1).

Abstract

Glioblastoma is one of the most difficult tumor types to treat with conventional therapy options like tumor debulking, chemo and radiotherapy. Immunotherapeutic agents like oncolytic viruses, immune checkpoint inhibitors and chimeric antigen receptor T cells have revolutionized cancer therapy, but their success in glioblastoma remains limited and further optimization of immunotherapies is needed. Several oncolytic viruses have demonstrated ability to infect tumors and trigger anti-tumor immune responses in malignant glioma patients. Leading the pack, oncolytic herpesvirus, first in its class, awaits an approval for treating malignant glioma from MHLW, the federal authority of Japan. Nevertheless, some major hurdles like the blood brain barrier, immunosuppressive tumor microenvironment, and tumor heterogeneity can engender suboptimal efficacy in malignant glioma. In this review, we discuss the current status of malignant glioma therapies with a focus on oncolytic viruses in clinical trials. Furthermore, we discuss the obstacles faced by oncolytic viruses in malignant glioma patients and strategies that are being used to overcome these limitations to 1) optimize delivery of oncolytic viruses beyond the blood brain barrier; 2) trigger inflammatory immune responses in and around tumors; and 3) use of multimodal therapies in combination to tackle tumor heterogeneity, with an end goal of optimizing the therapeutic outcome of oncolytic virotherapy.

Subject Areas

Glioblastoma; Oncolytic Virus; Blood Brain Barrier; Tumor Microenvironment; Tumor Heterogeneity

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