Glioblastoma (GBM) is a lethal primary malignant brain tumor with no current effective treatments.The recent emergence of immuno-virotherapy and FDA approval of T-VEC have generated a great expectation towards oncolytic herpes simplex viruses (oHSVs) as a promising treatment option for GBM.Since the generation and testing of the first genetically engineered oHSV in glioma in the early 1990s, oHSV-based therapies have shown a long way of great progress in terms of anti-GBM efficacy and safety, both preclinically and clinically.Here, we revisit the literature to understand the recent advancement of oHSV in the treatment of GBM.In addition, we discuss current obstacles to oHSVbased therapies and possible strategies to overcome these pitfalls.
Recent advancements in oncolytic virotherapy commend a special attention to developing new strategies for targeting cancer cells with oncolytic viruses (OVs). Modifications of the viral envelope or coat proteins serve as a logical mean of repurposing viruses for cancer treatment. In this review, we discuss how detailed structural knowledge of the interactions between OVs and their natural receptors provide valuable insights into tumor specificity of some viruses and re-targeting of alternate receptors for broad tumor tropism or improved tumor selectivity.
Purpose: Rhabdomyosarcomas (RMS) are difficult tumors to treat with conventional therapies. Publications indicate that oncolytic virotherapy (OV) could benefit cancer patients with tumors that are refractory to conventional treatments. It is believed that the efficacy of OV can be enhanced when used in combination with other treatments. This study evaluated the response of mice with aggressive alveolar RMS (ARMS) allografts to treatment with an OV [recombinant myxoma virus (MYXV Delta serp2)] in combination with a Janus kinase (JAK) inhibitor (oclacitinib). Oclacitinib is known to inhibit JAK1 and JAK2 cell signaling pathways, which should limit the antiviral Type I interferon response. However, oclacitinib does not inhibit immune pathways that promote antigen presentation, which help stimulate an anti-cancer immune response. Materials and Methods: To determine if MYXV Delta serp2 and oclacitinib could improve outcomes in animals with ARMS, nude mice were inoculated subcutaneously with murine ARMS cells to establish tumors Immune responses, tumor growth, and clinical signs in mice treated with combination therapy were compared to mice given placebo therapy and mice treated with OV alone. Results: Combination therapy was safe; no viral DNA was detected in off-target organs, only within tumors. As predicted, viral DNA was detected in tumors of mice given oclacitinib and MYXV Delta serp2 for a longer time period than mice treated with OV alone. Although tumor growth rates and median survival times were not significantly different between groups, clinical signs were less severe in mice treated with OV. Conclusion: Our data indicate that MYXV Delta serp2 treatment benefits mice with ARMS by reducing clinical signs of disease and improving quality of life.
Viruses have some characteristics in common with cell-based life. They can evolve and adapt to environmental conditions. Directed evolution can be used by researchers to produce viral strains with desirable phenotypes. Through bioselection, improved strains of oncolytic viruses can be obtained that have better safety profiles, increased specificity for malignant cells, and more efficient spread among tumor cells. It is also possible to select strains capable of killing a broader spectrum of cancer cell variants, so as to achieve a higher frequency of therapeutic responses. This review describes and analyses virus adaptation studies performed with members of four RNA virus families that are used for viral oncolysis: reoviruses, paramyxoviruses, enteroviruses, and rhabdoviruses.
