Recent Developments in Glioblastoma Therapy: Oncolytic Viruses and Emerging Future Strategies

Abstract

Glioblastoma is the most aggressive form of malignant brain tumor. Standard treatment protocols and traditional immunotherapy are poorly effective as they do not significantly increase the long-term survival of glioblastoma patients. Oncolytic viruses (OVs) may be an effective alternative approach. Combining OVs with some modern treatment options may also provide significant benefits for glioblastoma patients. Here we review virotherapy for glioblastomas and describe several OVs and their combination with other therapies. The personalized use of OVs and their combination with other treatment options would become a significant area of research aiming to develop the most effective treatment regimens for glioblastomas.

Tumor reduction after SARS‑CoV‑2 infection in a patient with lung cancer: A case report

“…Thus, if SARS-CoV-2 is to be used as an oncolytic therapy vector, a series of genetically engineered modifications need to be conducted. Similar to the case of combining poliovirus and rhinovirus to form a recombinant poliovirus chimera ( 24 ), it is necessary to further attenuate pathogenicity and cytotoxicity, and enhance specificity and security if SARS-CoV-2 is to play a role in antitumor immunomodulation.…”

Targeted Glioma Therapy—Clinical Trials and Future Directions

“…Oncolytic virotherapy is a novel approach for the targeted therapy of neoplasms that utilizes viruses for the elimination of tumor cells. While the exact mechanisms and the nature of tropism for such viruses might still be unknown, the main theories involve either direct killing of the targeted cells or indirect modulation of the host’s immune system response in order to mediate immunogenic cytotoxicity [ 158 , 159 ]. Clinical trials that have tested oncolytic virotherapy showed increased overall survival as compared with historical controls for polio-rhinovirus chimera PVSRIPO [ 160 ]; tumor reduction and safety were observed for tumor-replicative adenovirus DNX2401 with a median overall survival at 13 months for patients who received the treatment intratumorally [ 161 ].…”

Glioblastoma Therapy: Past, Present and Future

“…GB is particularly suitable for viral therapy to overcome TME immunosuppression and growth being surrounded mainly by post-mitotic cells, which allows the use of viruses that require active cell cycles for replication [ 835 ]. Viruses used to treat tumors can be divided into two categories: (1) oncolytic viruses (OVs) with the natural capacity to replicate only in cancer cells (reoviruses, and Newcastle disease viruses) or that are vulnerable to genetic manipulation that increases their tumor selectivity (adenoviruses, herpes simplex viruses, vaccina viruses, polioviruses, and measles viruses); and (2) viral vectors with a low replication rate, which are used as vehicles for other therapeutic genes [ 836 ]. Any of the viral categories can stimulate an immune response without the expression of an immunomodulatory transgene.…”

“…In addition, OVs have many advantages over conventional immunotherapies, including precise targeting, effective killing rates, and minimal adverse reactions [ 858 ]. To date, several clinical trials have been carried out for oncolytic viruses to improve the treatment of GB [ 836 , 843 , 857 ]. Examples include adenovirus [ 859 , 860 , 861 ], herpes simplex virus [ 862 , 863 , 864 ], reovirus [ 865 , 866 ], parvovirus [ 867 ], measles virus [ 868 , 869 , 870 ], poliovirus [ 853 , 871 ], vaccinia virus [ 872 ] and Newcastle disease virus [ 873 ].…”