Oncolytic Viruses as a Platform for the Treatment of Malignant Brain Tumors

Abstract

Malignant brain tumors remain incurable diseases. Although much effort has been devoted to improving patient outcome, multiple factors such as the high tumor heterogeneity, the strong tumor-induced immunosuppressive microenvironment, and the low mutational burden make the treatment of these tumors especially challenging. Thus, novel therapeutic strategies are urgent. Oncolytic viruses (OVs) are biotherapeutics that have been selected or engineered to infect and selectively kill cancer cells. Increasingly, preclinical and clinical studies demonstrate the ability of OVs to recruit T cells and induce durable immune responses against both virus and tumor, transforming a “cold” tumor microenvironment into a “hot” environment. Besides promising clinical results as a monotherapy, OVs can be powerfully combined with other cancer therapies, helping to overcome critical barriers through the creation of synergistic effects in the fight against brain cancer. Although many questions remain to be answered to fully exploit the therapeutic potential of OVs, oncolytic virotherapy will clearly be part of future treatments for patients with malignant brain tumors.

Mesenchymal stem cell carriers enhance anti‑tumor efficacy of oncolytic virotherapy (Review)

“…In TME, cancer-associated fibroblasts, adipocytes, Tregs, mesenchymal stromal cells and tumor-associated macrophages release numerous cytokines, such as IL-10, which support immune evasion and tumor growth ( 108 ). In recent years, oncolytic virotherapy (OVT) has been demonstrated to relieve the tumor immunosuppressive environments, and enhance anti-tumor immune responses ( 109 , 110 ). OVs stimulate anti-tumor immune responses which in turn, enhance the efficacy of immune checkpoint inhibitors (ICIs) ( 111 ).…”

The Current Status of Gene Therapy for the Treatment of Cancer

“…Oncolytic viruses act by directly lyses tumor cells and by introducing wild-type tumor suppressor genes into cells that lack the tumor suppressor gene. 48 , 49 Change in p53 gene function is present in half of all malignancies, and the induction of wild-type p53 gene re-establishes the normal p53 expression. Several recombinant OVs expressing p53 were developed with the aim of producing more potent OVs that act in combination with host immunity or with other treatments’ modality to destroy tumor cells.…”

“…Several recombinant OVs expressing p53 were developed with the aim of producing more potent OVs that act in combination with host immunity or with other treatments’ modality to destroy tumor cells. 49 , 50 …”

“…Administration of Imlygic causes apoptosis of tumor cell enhanced antigen presentation and increased antitumor response. 49 , 54 …”

Challenging Hurdles of Current Targeting in Glioblastoma: A Focus on Immunotherapeutic Strategies

“…Both trials report long term responders, and further clinical trials are awaited to potentially confirm significant survival efficacy. We refer the interested readers to the reference [ 110 ] for a detailed description of oncolytic viruses for GBM.…”