Oncolytic Virotherapy As Promising Immunotherapy Against Cancer: Mechanisms of Resistance to Oncolytic Viruses Publisher Pubmed



Goradel NH¹ ; Alizadeh A² ; Hosseinzadeh S³ ; Taghipour M⁴ ; Ghesmati Z⁵ ; Arashkia A⁶ ; Negahdari B¹ Show Affiliations
Source: Future Oncology Published:2022

Abstract

Oncolytic virotherapy has currently emerged as a powerful therapeutic approach in cancer treatment. Although the history of using viruses goes back to the early 20th century, the approval of talimogene laherparepvec (T-VEC) in 2015 increased interest in oncolytic viruses (OVs). OVs are multifaceted biotherapeutic agents because they replicate in and kill tumor cells and augment immune responses by releasing immunostimulatory molecules from lysed cells. Despite promising results, some limitations hinder the efficacy of oncolytic virotherapy. The delivery challenges and the upregulation of checkpoints following oncolytic virotherapy also mediate resistance to OVs by diminishing immune responses. Furthermore, the localization of receptors of viruses in the tight junctions, interferon responses, and the aberrant expression of genes involved in the cell cycle of the virus, including their infection and replication, reduce the efficacy of OVs. In this review, we present different mechanisms of resistance to OVs and strategies to overcome them. © 2021 Future Medicine Ltd.