# Oncolytic Virus Therapies in Malignant Gliomas: Advances and Clinical Trials

## TL;DR

This review explores oncolytic viruses as a potential treatment for brain cancers like glioblastoma, highlighting their progress in preclinical and clinical studies.

## Contribution

The paper provides a comprehensive review of oncolytic virus therapies for brain tumors, emphasizing recent clinical and preclinical advancements.

## Key findings

- Oncolytic viruses like HSV-1, adenovirus, and poliovirus show therapeutic potential in treating brain cancers.
- Combining these viruses with immune modulating strategies has been explored in clinical trials.
- Further research is needed to understand the biological interactions in the brain tumor microenvironment.

## Abstract

The current prognosis for primary brain cancers such as glioblastoma remains poor despite aggressive clinical measures. Immunotherapy has demonstrated promise in the treatment of many other types of cancers, but this has not been apparent when it comes to brain malignancies. This has necessitated exploring other immune modulating methodologies, one of which has been the utilization of cancer-targeted viruses, also known as oncolytic viruses. In this review, we summarize the progress this field has made in both the preclinical space, which interrogates the still lesser-known biology of brain tumors, as well as the clinical space, through a number of trials that give insight into the therapeutic applicability of a particle that is otherwise a pathogen. By doing so, we hope to provide insight into future directions for expanded treatment options for this patient population.

The overall survival rate of brain malignancies such as glioblastoma is currently a little under two years, at most, and treatment options for malignant brain tumors have demonstrated limited efficacy. The current standard of care to treat brain cancer includes surgical resection, radiation, and chemotherapy. Historically, an observed interaction between malignancies and concurrent viral infection has shown therapeutic potential that can perhaps be better leveraged in brain cancer with the technological advances that we have today. We aim to discuss a variety of viral vector designs to harness their oncolytic potential and explore how some of these ideas have performed in clinical trials. In our review, three major viral candidates that have gained traction in this field of research—Herpes simplex virus-1, adenovirus, and poliovirus—are highlighted. How the field has manipulated aspects of their virology and combined these viral platforms with other immune modulating strategies to treat both adult and pediatric tumors is also surveyed. Finally, the work exploring the possibility of other neurotropic viral candidates has been elaborated. More insight into the biological interactions between tumor, brain, and body is needed to address this particularly difficult clinical challenge. While there is still no clear, effective treatment for brain malignancies, the utilization of oncolytic viruses shows potential both as a treatment and as a tool to better understand the immune microenvironment of this pathology.