Abstract

Simple SummaryOncolytic viruses (OVs) are viruses that selectively target and kill cancer cells while sparing normal ones. OVs are from diverse families of viruses, but naturally occurring OVs have been genetically engineered due to their limitations in therapeutic application. These engineered OVs with enhanced tumor targeting ability, oncolytic activity, or generating potent anti-tumor immune responses are tested in preclinical animal models and cancer patients in clinical trials. Due to their multi-mechanistic anti-tumor effects, OVs have emerged one of the key cancer immunotherapy agents. However, due to the limited success with novel anti-cancer therapies such as immunotherapies and cell-based therapies, combination therapies should be tested with OVs. We discuss such combination therapies that are explored to further improve oncolytic virotherapy.Cancer remains a leading cause of death worldwide. Despite many signs of progress, currently available cancer treatments often do not provide desired outcomes for too many cancers. Therefore, newer and more effective therapeutic approaches are needed. Oncolytic viruses (OVs) have emerged as a novel cancer treatment modality, which selectively targets and kills cancer cells while sparing normal ones. In the past several decades, many different OV candidates have been developed and tested in both laboratory settings as well as in cancer patient clinical trials. Many approaches have been taken to overcome the limitations of OVs, including engineering OVs to selectively activate anti-tumor immune responses. However, newer approaches like the combination of OVs with current immunotherapies to convert “immune-cold” tumors to “immune-hot” will almost certainly improve the potency of OVs. Here, we discuss strategies that are explored to further improve oncolytic virotherapy.

Highlights

  • Rigvir (ECHO-7) Picornavirus Human Latvia Melanoma Unmodified Oncorine (H101)Adenovirus serotype 5 ChinaHead and neck cancerDeleted for viral

  • Engineering of Oncolytic viruses (OVs) with different approaches enhanced oncolytic activity and activated the antitumor immune responses, better therapeutic outcomes were reported when oncolytic viruses were used in combination with other cancer treatment modalities, such as chemotherapy, radiation therapy, immunotherapy, or cell therapy [96,97,98]

  • OVs, genetically engineered OVs, can enhance lymphocyte infiltration and activation as well as lysis of cancer cells. To overcome this lack of immune checkpoint inhibitors (ICIs) effectiveness in too many patients, OV virotherapy combined with ICIs has been tested in preclinical models and clinical trials, and has shown promising results [114,115,116,117] OVs that are currently under clinical trials in combination with ICIs are herpes simplex virus (HSV) (OH2), vaccinia virus (VACV) (PexaVec), Reovirus (Reolysin), Adenovirus (LOAd703), Newcastle disease virus (NDV) (MEDI5395), and Vesicular stomatitis virus (VSV) (VSV-IFNbNIS) (Table 3)

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Summary

Oncolytic Virus

Oncolytic viruses (OVs) were selected for development because they can selectively infect and kill cancer cells but spare their normal cellular counterparts. Oncolytic virotherapy received even more attention after realizing that the true potential of viruses in cancer therapy lies in the ability to trigger novel cancer-specific acquired immune responses against tumor antigens. These observations have shifted the application of OVs from purely lytic agents to antitumor immune-activating agents, and the field could be more correctly called “oncolytic immunotherapy”. Another newer aspect of OV is their potential application in combination therapy with traditional and modern cancer treatment modalities, with immune checkpoint inhibitors (ICIs) and T cell-based therapies

Background
Overexpression of Receptor Molecules on the Cancer Cell Surface
Alteration in Intracellular Signaling Pathways
Altered Metabolism of Cancer Cells
Mechanisms of Antitumor Effects Mediated by OVs
Engineered Oncolytic Viruses
Combination Therapy with Oncolytic Virus
Combination with Traditional Radiotherapy and Chemotherapy
Systemic Delivery of OV via Carrier Cells
Combination with Cell Therapy
Conclusions
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