Oncolytic immunovirotherapy for high-grade gliomas: A novel and an evolving therapeutic option

Abstract

Glioblastoma is one of the most difficult tumor types to manage, having high morbidity and mortality with available therapies (surgery, radiotherapy and chemotherapy). Immunotherapeutic agents like Oncolytic Viruses (OVs), Immune Checkpoint Inhibitors (ICIs), Chimeric Antigen Receptor (CAR) T cells and Natural Killer (NK) cell therapies are now being extensively used as experimental therapies in the management of glioblastoma. Oncolytic virotherapy is an emerging form of anti-cancer therapy, employing nature’s own agents to target and destroy glioma cells. Several oncolytic viruses have demonstrated the ability to infect and lyse glioma cells by inducing apoptosis or triggering an anti-tumor immune response. In this mini-review, we discuss the role of OV therapy (OVT) in malignant gliomas with a special focus on ongoing and completed clinical trials and the ensuing challenges and perspectives thereof in subsequent sections.

Mesenchymal Stem Cell (MSC)-Based Drug Delivery into the Brain across the Blood–Brain Barrier

“…Oncolytic viruses selectively infect cancer cells and eventually lyse them without infecting healthy cells [ 42 ]. In fact, glioma cells were destroyed by oncolytic viruses [ 43 ]. Teserpaturev (G47Δ, Delytact), a third generation (triple-mutated) recombinant oncolytic herpes simplex virus type 1, was conditionally approved for malignant glioma in June 2021 in Japan [ 44 ].…”

Microglia-mediated drug substance transfer promotes chemoresistance in brain tumors: insights from an in vitro co-culture model using GCV/Tk prodrug system

“…Moreover, our observation of chemo-substance transfer from glioma cells to microglia cells suggests the intriguing possibility that microglia cells could potentially safeguard glioma cells. From conventional ROS-accumulated radiation therapy to innovative approaches like oncolytic virus therapy, where tumor cells are overloaded with the virus to trigger apoptosis and subsequently the antitumor response from infiltrated immune cells [ 61 , 62 ]. This intriguing avenue invites further investigation in not only the murine model but human or clinical model to the complex mutual interactions between microglia and glioma cells across a spectrum of therapeutic modalities.…”

Bioengineered Mesenchymal Stem/Stromal Cells in Anti-Cancer Therapy: Current Trends and Future Prospects

“…Oncolytic viruses (OV) are attenuated, non-pathogenic viruses designed to selectively recognize, infect and destroy tumour cells without affecting the rest of the healthy cell types where they are unable to replicate [105,119,147]. Its therapeutic use began at the end of the 19th century, with some controversy due to the poor clinical outcomes observed in early cancer patient trials.…”

“…However, viruses from other animal species, such as Newcastle virus, vesicular stomatitis virus or retroviruses, can also be used, and more than 10 viral families with their serotypes and subgroups have been studied as anti-tumour therapeutic agents [149][150][151][152]. Their mechanisms of action are dual, based on: (1) the selective destruction of tumour cells after infection (direct cellular oncolysis); and (2) the stimulation of the patient systemic anti-tumour immunity induced by the release of new viral particles generated by the lysis of tumour cells, which create a more pro-inflammatory tumour microenvironment that favours the immune attack and limits the evasion capacity of tumour cells (indirect cellular oncolysis) [105,119,147,148,151,153].…”

“…Unfortunately, these anti-cancer effects associated with oncolytic virus may be reduced when administered systemically intravenously, resulting in more occasional and transient responses than when administered locally (intratumorally) [154]. The main factors associated with this low anti-tumour efficacy after intravenous administration are (1) the ability of the patient immune system to recognize and neutralize the oncolytic viruses before they can reach the tumour and exert their therapeutic effects; (2) the presence of an inadequate tropism, whereby these oncolytic viruses are directed to tissues where they can be trapped or retained, such as the liver or spleen; (3) the presence of factors associated with the tumour development; and (4) the occurrence of factors associated with the tumour microenvironment that prevent their pre-penetration and intratumoural diffusion, including the release of chemokines and cytokines such as IL-10 and transforming growth factor β (TGF-β), among others [105,119,147,148,150,154].…”