Oncolytic Virotherapy for the Treatment of Malignant Glioma

Abstract

Malignant glioma is the most common primary brain tumor and carries a grim prognosis, with a median survival of just over 14 months. Given the poor outcomes with standard-of-care treatments, novel treatment strategies are needed. The concept of virotherapy for the treatment of malignant tumors dates back more than a century and can be divided into replication-competent oncolytic viruses and replication-deficient viral vectors. Oncolytic viruses are designed to selectively target, infect, and replicate in tumor cells, while sparing surrounding normal brain. A host of oncolytic viruses has been evaluated in early phase human trials with promising safety results, but none has progressed to phase III trials. Despite the 25 years that has passed since the initial publication of genetically engineered oncolytic viruses for the treatment of glioma, much remains to be learned about the use of this therapy, including its mechanism of action, optimal treatment paradigm, appropriate targets, and integration with adjuvant agents. Oncolytic viral therapy for glioma remains promising and will undoubtedly impact the future of patient care.

Intratumoral Immunotherapy—Update 2019

“…PVS‐RIPO (Istari Oncology Inc., Research Triangle Park, NC) is a recombinant nonpathogenic poliovirus derived from the live attenuated Sabin poliovirus vaccine. To minimize the neurovirulence of wild‐type poliovirus, PVS‐RIPO is genetically modified with a heterologous human rhinovirus type 2 internal ribosomal entry site, which preferentially blocks viral translation in neurons while maintaining affinity for tumor cells .…”

Development of oncolytic virotherapy: from genetic modification to combination therapy

“…For example, adenovirus type 5 (Ad5) is a widely used OV vector, but its receptor, coxsackie adenovirus receptor (CAR), is not highly expressed in many tumor cells [22]; this phenomenon leads to the low entry efficiency of OAd. Through genetic engineering, an arginine-glycine-aspartic acid (RGD) motif was inserted into the fiber knob domain of Ad5 to generate a newly modified virus, which no longer depends on CAR to enter tumor cells and instead relies on integrins that are highly expressed on tumor cells, to enter tumor cells [82]. Other studies inserted the fiber knob domain derived from adenovirus type 3 (Ad3) into the backbone of Ad5 (also named serotype switching) to allow its entrance to the tumor cells by utilizing the highly expressed Ad3 receptor (desmoglein 2 as the primary receptor) on tumor cells to enter the tumor cells [79].…”

Challenging the indiscriminate use of temozolomide in pediatric high‐grade gliomas: A review of past, current, and emerging therapies

“…Oncolytic viruses confer their antitumor activity through direct cancer cell lysis and by induction of both the innate and adaptive antitumor immune responses . A small number of studies have focused on oncolytic virotherapy for pHGG …”

“…Oncolytic virotherapy uses viruses to selectively destroy cancer cells 73 and is gathering momentum as a novel approach for pHGG. 74,75 Oncolytic viruses confer their antitumor activity through direct cancer cell lysis and by induction of both the innate and adaptive antitumor immune responses. 74,76 A small number of studies have focused on oncolytic virotherapy for pHGG.…”

“…74,76 A small number of studies have focused on oncolytic virotherapy for pHGG. 74,75 Herpes simplex virus-1 G207 has been delivered by continuous infusion via intratumoral catheters to pediatric patients with recurrent malignant supratentorial tumors. 77 This strategy is currently being evaluated in a phase I trial with/without a single fraction of radiotherapy in children with relapsed malignant supratentorial brain tumors (NCT02457845).…”