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Paramyxoviruses for Tumor-targeted Immunomodulation: Design and Evaluation Ex Vivo
Published on: January 7, 2019
Design and application of oncolytic HSV vectors for glioblastoma therapy
Paola Grandi1, Pierpaolo Peruzzi, Bonnie Reinhart
1Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA. pag24@pitt.edu
Abstract:
Glioblastoma multiforme is one of the most common human brain tumors. The tumor is generally highly infiltrative, making it extremely difficult to treat by surgical resection or radiotherapy. This feature contributes to recurrence and a very poor prognosis. Few anticancer drugs have been shown to alter rapid tumor growth and none are ultimately effective. Oncolytic vectors have been employed as a treatment alternative based on the ability to tailor virus replication to tumor cells. The human neurotropic herpes simplex virus (HSV) is especially attractive for development of oncolytic vectors (oHSV) because this virus is highly infectious, replicates rapidly and can be readily modified to achieve vector attenuation in normal brain tissue. Tumor specificity can be achieved by deleting viral genes that are only required for virus replication in normal cells and permit mutant virus replication selectively in tumor cells. The anti-tumor activity of oHSV can be enhanced by arming the vector with genes that either activate chemotherapeutic drugs within the tumor tissue or promote anti-tumor immunity. In this review, we describe current designs of oHSV and the experience thus far with their potential utility for glioblastoma therapy. In addition, we discuss the impediments to vector effectiveness and describe our view of future developments in vector improvement.
Insights
Oncolytic herpes simplex virus (oHSV) vectors show promise for treating glioblastoma multiforme. These engineered viruses selectively target and replicate in tumor cells, offering a novel therapeutic strategy for this aggressive brain cancer.
Area of Science:
- Neuro-oncology
- Virology
- Biotechnology
Background:
- Glioblastoma multiforme is a highly infiltrative and aggressive human brain tumor with poor prognosis.
- Current treatments like surgery and radiotherapy have limited efficacy due to tumor infiltration and recurrence.
- Few drugs effectively alter glioblastoma growth, necessitating novel therapeutic approaches.
Purpose of the Study:
- To review current designs of oncolytic herpes simplex virus (oHSV) vectors for glioblastoma therapy.
- To discuss the potential utility and limitations of oHSV in treating glioblastoma.
- To explore future developments in oHSV vector improvement for enhanced anti-tumor activity.
Main Methods:
- Review of existing literature on oncolytic virus therapy, specifically focusing on engineered herpes simplex virus (HSV).
- Analysis of strategies for achieving tumor specificity by modifying viral genes for selective replication in cancer cells.
- Examination of methods for enhancing anti-tumor activity, including drug activation and immune stimulation.
Main Results:
- Oncolytic HSV (oHSV) vectors can be engineered for tumor-specific replication by deleting viral genes essential for normal cell replication.
- oHSV vectors can be armed with therapeutic genes to enhance anti-tumor effects, such as activating chemotherapeutics or promoting anti-tumor immunity.
- Current oHSV designs show potential for glioblastoma treatment, but impediments to vector effectiveness require further investigation.
Conclusions:
- Engineered oncolytic herpes simplex virus (oHSV) represents a promising therapeutic avenue for glioblastoma multiforme.
- Strategies involving tumor-specific replication and gene-arming enhance oHSV's anti-cancer potential.
- Further research and development are crucial to overcome existing challenges and optimize oHSV for clinical application in brain tumor treatment.

