Exploring Reovirus Plasticity for Improving Its Use as Oncolytic Virus

Abstract

Reoviruses are non-enveloped viruses with a segmented double stranded RNA genome. In humans, they are not associated with serious disease. Human reoviruses exhibit an inherent preference to replicate in tumor cells, which makes them ideally suited for use in oncolytic virotherapies. Their use as anti-cancer agent has been evaluated in several clinical trials, which revealed that intra-tumoral and systemic delivery of reoviruses are well tolerated. Despite evidence of anti-tumor effects, the efficacy of reovirus in anti-cancer monotherapy needs to be further enhanced. The opportunity to treat both the primary tumor as well as metastases makes systemic delivery a preferred administration route. Several pre-clinical studies have been conducted to address the various hurdles connected to systemic delivery of reoviruses. The majority of those studies have been done in tumor-bearing immune-deficient murine models. This thwarts studies on the impact of the contribution of the immune system to the tumor cell eradication. This review focuses on key aspects of the reovirus/host-cell interactions and the methods that are available to modify the virus to alter these interactions. These aspects are discussed with a focus on improving the reovirus’ antitumor efficacy.

Enhanced Killing of Triple-Negative Breast Cancer Cells by Reassortant Reovirus and Topoisomerase Inhibitors

“…Reovirus has an inherent preference to replicate in tumor cells, making it ideally suited for use in oncolytic therapy (15, 16). Reovirus can be delivered to patients via intratumoral and intravenous administration and can be effective in combination therapy (14).…”

“…Reovirus can be delivered to patients via intratumoral and intravenous administration and can be effective in combination therapy (14). Reovirus has an inherent preference to replicate in tumor cells, making it ideally suited for use in oncolytic virotherapies (15, 16). However, the cellular and viral factors that promote preferential reovirus infection of cancer cells are not fully elucidated.…”

Oncolytic reovirus shows potentially anticancer effect against CT26 cell lines

“…Oncolytic reoviruses due to selectively replication and triggering anti-cancer responses into the cancer cells with low pathogenicity in normal cells, was considered as an anti-cancer option by scientists [2,3]. Recently most clinical trials have focused on T3D strain (Reolysine) because of its maximum oncolysis effect among the other reovirus strains against several cancers [5].…”

“…Oncolytic reovirus (Respiratory Enteric Orphan viruses) is a small non-enveloped virus, which commonly, isolated from respiratory and gastrointestinal tract without any known and severs disease [4]. Reovirus has three strains (Dearing, long, Jones) with anti-tumor properties, but most clinical trials have recently focused on the T3D strain (Reolysine) [5,6]. The viral ligand in all strains is the Sigma 1 protein attached to the Junction adhesion molecule A (JAM-A) receptor in the long and Jones strains, but T3D strain beside this receptor (JAM-A), can use from Nogo receptor1 (NgR1) for virus attachment and entrance to the host cells [5].…”

“…Therefore, developing of new approaches for treatment of colon cancer is urgently needed. Distinct features of oncolytic reovirus including: high infectivity and virus production rate, proper cell cultures and hosts, easily virus manipulation, selectively infection and apoptosis induction in the cancer cells caused introduce this agent as promising antitumor candidate [18][19][20].…”