Oncolytic virotherapy using herpes simplex virus: how far have we come?

Sokolowski, Nicolas A. S.; Rizos, Helen; Diefenbach, Russell J.

doi:10.2147/ov.s66086

Cited by 21 publications

(16 citation statements)

References 137 publications

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“…This includes but is not limited to, actin remodelling during viral surfing prior to entry (and most likely exit), transport along microtubules to deliver viral components to and from the nucleus and for axonal transport during initial viral uptake into the sites of latency or reactivation. Certainly, in the context of cytoskeleton regulation and subversion of molecular motors by alphaherpesviruses our increasing knowledge will not only provide targets for new antivirals but inform on attenuated virus design for gene therapy [ 191 ], oncolytic virotherapy [ 27 ] and vaccine development [ 157 ].…”

Section: Discussionmentioning

confidence: 99%

“…Current antivirals target DNA replication during the viral lifecycle but new mechanisms and the advent of combination therapies may lead to better patient outcomes. Furthermore, HSV has been targeted for use as a viable gene therapy vehicle and is used in the field of oncolytic virotherapy for the treatment of solid tumours [ 27 , 28 ]. Therefore, further investigation of the crucial virus-host interactions involved during the lifecycles of these alphaherpesviruses will pull the cytoskeletons from the closet; the discovery of these unknown mechanisms will benefit the understanding of alphaherpesvirus reactivation pathways and potentially lead to novel therapeutic options.…”

Section: Herpesvirusesmentioning

confidence: 99%

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Cytoskeletons in the Closet—Subversion in Alphaherpesvirus Infections

Denes

Miranda-Saksena

Cunningham

et al. 2018

Viruses

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Actin filaments, microtubules and intermediate filaments form the cytoskeleton of vertebrate cells. Involved in maintaining cell integrity and structure, facilitating cargo and vesicle transport, remodelling surface structures and motility, the cytoskeleton is necessary for the successful life of a cell. Because of the broad range of functions these filaments are involved in, they are common targets for viral pathogens, including the alphaherpesviruses. Human-tropic alphaherpesviruses are prevalent pathogens carried by more than half of the world’s population; comprising herpes simplex virus (types 1 and 2) and varicella-zoster virus, these viruses are characterised by their ability to establish latency in sensory neurons. This review will discuss the known mechanisms involved in subversion of and transport via the cytoskeleton during alphaherpesvirus infections, focusing on protein-protein interactions and pathways that have recently been identified. Studies on related alphaherpesviruses whose primary host is not human, along with comparisons to more distantly related beta and gammaherpesviruses, are also presented in this review. The need to decipher as-yet-unknown mechanisms exploited by viruses to hijack cytoskeletal components—to reveal the hidden cytoskeletons in the closet—will also be addressed.

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Section: Discussionmentioning

confidence: 99%

Section: Herpesvirusesmentioning

confidence: 99%

Cytoskeletons in the Closet—Subversion in Alphaherpesvirus Infections

Denes

Miranda-Saksena

Cunningham

et al. 2018

Viruses

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“… 40 These viruses have a large genome that is amenable to genetic manipulation and the insertion of therapeutic genes, making them an attractive platform for the development of novel virus-based therapies. Several distinct oHSVs have been engineered by investigators and pharmaceutical companies, 41 – 45 including the recently FDA-approved oHSV talimogene laherparepvec (T-VEC) for the treatment of melanoma. 46 Multiple preclinical and early-phase clinical trials have shown that combining these agents with PD-1/PD-L1 blockade can be beneficial.…”

Section: Combination Of Oncolytic Dna Viruses With Pd-1/pd-l1 Checkpomentioning

confidence: 99%

Oncolytic virus and PD-1/PD-L1 blockade combination therapy

Chen

Hutzen

Wedekind

et al. 2018

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Oncolytic viruses are lytic for many types of cancers but are attenuated or replication-defective in normal tissues. Aside from tumor lysis, oncolytic viruses can induce host immune responses against cancer cells and may thus be viewed as a form of immunotherapy. Although recent successes with checkpoint inhibitors have shown that enhancing antitumor immunity can be effective, the dynamic nature of the immunosuppressive tumor microenvironment presents significant hurdles to the broader application of these therapies. Targeting one immune-suppressive pathway may not be sufficient to eliminate tumors. Here we focus on the development of the combination of oncolytic virotherapy with checkpoint inhibitors designed to target the programmed cell death protein 1 and programmed cell death ligand 1 signaling axis. We also discuss future directions for the clinical application of this novel combination therapy.

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“…HSV-1, belonging to family Herpesviridae of neurotropic dsDNA viruses, is a causative agent of a self-limiting disease. Due to its cytolytic replication cycle and easily modified large genome, HSV-1 is beneficial as an oncolytic agent [ 62 , 63 ]. Moreover, HSV-1 infects different cell types, and the presence of a separate attachment and fusion glycoproteins within its envelope is beneficial for modification to improve tumor targeting [ 63 ].…”

Section: Ovs and Nf-κbmentioning

confidence: 99%

NF-κB Signaling in Targeting Tumor Cells by Oncolytic Viruses—Therapeutic Perspectives

Struzik

Szulc-Dąbrowska

2018

Cancers

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In recent years, oncolytic virotherapy became a promising therapeutic approach, leading to the introduction of a novel generation of anticancer drugs. However, despite evoking an antitumor response, introducing an oncolytic virus (OV) to the patient is still inefficient to overcome both tumor protective mechanisms and the limitation of viral replication by the host. In cancer treatment, nuclear factor (NF)-κB has been extensively studied among important therapeutic targets. The pleiotropic nature of NF-κB transcription factor includes its involvement in immunity and tumorigenesis. Therefore, in many types of cancer, aberrant activation of NF-κB can be observed. At the same time, the activity of NF-κB can be modified by OVs, which trigger an immune response and modulate NF-κB signaling. Due to the limitation of a monotherapy exploiting OVs only, the antitumor effect can be enhanced by combining OV with NF-κB-modulating drugs. This review describes the influence of OVs on NF-κB activation in tumor cells showing NF-κB signaling as an important aspect, which should be taken into consideration when targeting tumor cells by OVs.

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Oncolytic virotherapy using herpes simplex virus: how far have we come?

Cited by 21 publications

References 137 publications

Cytoskeletons in the Closet—Subversion in Alphaherpesvirus Infections

Cytoskeletons in the Closet—Subversion in Alphaherpesvirus Infections

Oncolytic virus and PD-1/PD-L1 blockade combination therapy

NF-κB Signaling in Targeting Tumor Cells by Oncolytic Viruses—Therapeutic Perspectives

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