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Oncolytic Viruses in Glioma Treatment

Introduction of Glioma

Glioma is a type of tumor that occurs in the brain and spinal cord. Gliomas begin in the glial cells that surround nerve cells and help them function. Gliomas are classified according to the type of glial cells involved in the tumor, as well as the tumor's genetic features. There are three types of glial cells can produce tumors, including astrocytomas (such as astrocytoma, anaplastic astrocytoma and glioblastoma), ependymomas (such as anaplastic ependymoma, myxopapillary ependymoma and subependymoma), and oligodendrogliomas (such as oligodendroglioma, anaplastic oligodendroglioma and anaplastic oligoastrocytoma). Common signs and symptoms of gliomas include headache, nausea or vomiting, confusion or a decline in brain function, memory loss, personality changes or irritability, difficulty with balance, urinary incontinence, vision problems, speech difficulties and seizures. Malignant glioma is the most common primary brain tumor and carries a grim prognosis, with a median survival of about 14 months. Given the poor outcomes with standard-of-care treatments including radiotherapy, chemotherapy and surgery when possible, novel treatment strategies are needed.

Oncolytic Viruses in Glioma Treatment

Oncolytic Viruses for the Treatment of Glioma

The concept of virotherapy for the treatment of malignant tumors dates back more than a century. Unique to oncolytic viruses is the ability of the virus to infect specifically a tumor cell and induce tumor lysis through the release of viral progeny, which can subsequently infect nearby tumor cells. Until now, several oncolytic viruses have advanced to clinical trials, including adenovirus, herpes simplex virus (HSV), Newcastle disease virus (NDV), reovirus, parvovirus H-1 (H-1PV), measles virus, and poliovirus. Table 1 presents completed oncolytic virus trials and there are still many others are at advanced preclinical stages.

Study phase Disease Experimental therapy Results
Case report Recurrent GBM MTH-68/h: live attenuated NDV No significant toxicity; neurologic improvement; progressive tumor shrinkage
Case series Progressive high-grade glioma MTH-68/h: live attenuated NDV No adverse effects; neurologic improvement; tumor shrinkage
Case report Recurrent anaplastic astrocytoma MTH-68/h: live attenuated NDV+valproic acid Partial tumor response; oncolytic activity a result of viral replication
I Recurrent malignant glioma HSV171:ICP34.5-deleted HSV No adverse clinical symptoms, encephalitis, or reactivation of latent virus
I Malignant glioma HSV1716: ICP34.5-deleted HSV No toxicity; evidence of viral replication in tumor
I High-grade glioma HSV1716: ICP34.5-deleted HSV No toxicity; encouraging imaging data
I Recurrent malignant glioma G207: ICP6-inactivated and ICP34.5-deleted HSV No viral-related toxicity; evidence of antitumor activity
Ib Recurrent GBM G207: ICP6-inactivated and ICP34.5-deleted HSV No encephalitis; evidence of antitumor activity and viral replication
I Malignant glioma G207: ICP6-inactivated and ICP34.5-deleted HSV + radiation Treatment well tolerated; 3 instances of marked radiographic response
I Recurrent malignant glioma ONYX-015: E1B and E3-deleted adenovirus No serious virus-related adverse events; MTD was not reached
I/II Recurrent GBM NDV-HJU: lentogenic NDV Minimal toxicity; MTD not achieved; 1 patient with complete response
I Recurrent malignant glioma Reolysin: reovirus No serious adverse events related to treatment; MTD was not reached
I Recurrent malignant glioma Reolysin: reovirus DLT not identified; MTD not reached; evidence of anti-glioma activity

Table 1. Completed oncolytic virotherapy trials for the treatment of malignant glioma. (Foreman, 2017)

25 years have passed since the initial publication of genetically engineered oncolytic viruses for the treatment of glioma. Oncolytic viral therapy for glioma remains promising and will undoubtedly impact the future of patient care. Creative Biolabs has successfully developed the OncoVirapy™ platform and we offer a one-stop solution for a broad range of oncolytic virus construction and oncolytic virus engineering scope.

Reference

  1. Foreman, P.M.; et al. Oncolytic virotherapy for the treatment of malignant glioma. Neurotherapeutics. 2017, 14(2):333-44.

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