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.
Highlights
Malignant primary brain tumors represent one of the most difficult cancers to treat, leading to significant cancer-related morbidity and mortality in both children and adults
G47∆ was generated by adding another deletion mutation to ICP47, a protein that inhibits peptide loading onto major histocompatibility complex (MHC) class I molecules on the surface of virus-infected cells
Martínez-Velez et al demonstrated that combining the Delta-24-arginyl-glycil-aspartic acid motif (RGD) virus with radiotherapy resulted in a synergistic antiglioma activity in vitro and in vivo in pediatric high-grade glioma and diffuse intrinsic pontine glioma (DIPG) models [135]
Summary
Malignant primary brain tumors represent one of the most difficult cancers to treat, leading to significant cancer-related morbidity and mortality in both children and adults. Glioblastomas (GBM) are endowed with the poorest overall survival, with
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