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Growth, Purification, and Titration of Oncolytic Herpes Simplex Virus
Published on: May 13, 2021
Combinatorial strategies for oncolytic herpes simplex virus therapy of brain tumors
Abstract:
Oncolytic viruses, such as the oncolytic herpes simplex virus (oHSV), are an exciting new therapeutic strategy for cancer as they are replication competent in tumor cells but not normal cells. In order to engender herpes simplex virus with oncolytic activity and make it safe for clinical application, mutations are engineered into the virus. Glioblastoma multiforme (GBM) is the most common and deadly primary brain tumor in adults. Despite many advances in therapy, overall survival has not been substantially improved over the last several decades. A number of different oHSVs have been tested as monotherapy in early-phase clinical trials for GBM and have demonstrated safety and anecdotal evidence of efficacy. However, strategies to improve efficacy are likely to be necessary to successfully treat GBM. Cancer treatment usually involves multimodal approaches, so the standard of care for GBM includes surgery, radiotherapy and chemotherapy. In preclinical GBM models, combinations of oHSV with other types of therapy have exhibited markedly improved activity over individual treatments alone. In this review, we will discuss the various combination strategies that have been employed with oHSV, including chemotherapy, small-molecule inhibitors, antiangiogenic agents, radiotherapy and expression of therapeutic transgenes. Effective combinations, especially synergistic ones, are clinically important not just for improved efficacy but also to permit lower and less-toxic doses and potentially overcome resistance.
Insights
Oncolytic herpes simplex virus (oHSV) shows promise for treating glioblastoma multiforme (GBM). Combining oHSV with other therapies significantly enhances anti-tumor activity, offering new hope for this deadly brain cancer.
Area of Science:
- Oncolytic virotherapy
- Neuro-oncology
- Cancer genomics
Background:
- Oncolytic viruses, like engineered herpes simplex virus (oHSV), selectively replicate in tumor cells.
- Glioblastoma multiforme (GBM) remains a highly lethal primary brain tumor with limited therapeutic advancements.
- Current oHSV therapies show safety and some efficacy in early GBM trials, but improved strategies are needed.
Purpose of the Study:
- To review combination strategies for enhancing oncolytic herpes simplex virus (oHSV) efficacy in glioblastoma multiforme (GBM) treatment.
- To explore how combining oHSV with other therapies can overcome treatment resistance and improve patient survival.
- To highlight the potential of multimodal approaches in neuro-oncology.
Main Methods:
- Review of preclinical studies and clinical trials involving oncolytic herpes simplex virus (oHSV) for glioblastoma multiforme (GBM).
- Analysis of combination therapies including chemotherapy, small-molecule inhibitors, antiangiogenic agents, and radiotherapy.
- Examination of transgene expression strategies to augment oHSV activity.
Main Results:
- Preclinical models demonstrate significantly enhanced anti-GBM activity when oHSV is combined with other therapeutic modalities.
- Combination therapies show potential for synergistic effects, leading to improved tumor cell killing.
- Evidence suggests that combination strategies can overcome resistance mechanisms and improve overall treatment outcomes.
Conclusions:
- Combining oncolytic herpes simplex virus (oHSV) with standard or novel therapies offers a promising strategy to improve glioblastoma multiforme (GBM) treatment efficacy.
- Synergistic combinations can potentially reduce treatment toxicity and overcome therapeutic resistance.
- Multimodal approaches integrating oHSV are crucial for advancing GBM therapy and improving patient survival.
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