Oncolytic Viral Therapy of Glioblastoma: Will this Soon become a Reality?

Abstract

The first oncolytic virus therapy (talimogene laherparepvec or TVEC) in the U.S. was approved in October 2015 for the treatment of advanced melanoma patients [1]. Such novel and safer treatments are in active development but not yet available for brain tumors. Glioblastoma multiforme (GBM) is the most common and aggressive form of brain cancer in adults with median survival of less than 15 months [2]. Current radiotherapy and chemotherapy regimens not only have failed to significantly benefit high-grade tumor patients, but also are associated with severe long-term side effects that worsen the quality of life. The development of more effective and tumor-selective treatment modalities is urgently needed. In the last decade, oncolytic viruses (OV) have emerged as a potential cancer therapeutic agent. Ovs are replication-competent viruses that selectively infect and replicate in cancer cells harboring a multitude of genetic alterations that allows virus propagation. The virus then either directly disrupts tumor cells further releasing infectious virions, or indirectly stimulates the host’s immune system to mount a sustainable anti-tumor response. Compared to conventional chemotherapy, advantages of OVs are two fold; 1) the incompetence of OVs to grow in normal cells due to intact anti-viral response and apoptotic pathways results in minimized sideeffects, and 2) OVs self-amplify and the infection increases within and between tumor cells with time [3,4]. The clinical testing of oncolytic viruses