Oncolytic virotherapy

Russell, Stephen J.; Peng, Kah-Whye; Bell, John C.

doi:10.1038/nbt.2287

Cited by 1,214 publications

(1,400 citation statements)

References 160 publications

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“…8 Moreover, proinflammatory cytokines generated in the virus-infected cancer cells can restore the immunosuppressive tumor microenvironment. [9][10][11] Thus, oncolytic viruses are recently viewed as anticancer immunotherapeutic agents. These backgrounds make it imperative to update the molecular pathways and/or cellular constituents that regulate ICD.…”

Section: Open Questionsmentioning

confidence: 99%

Multimodal immunogenic cancer cell death as a consequence of anticancer cytotoxic treatments

2013

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Apoptotic cell death generally characterized by a morphologically homogenous entity has been considered to be essentially non-immunogenic. However, apoptotic cancer cell death, also known as type 1 programmed cell death (PCD), was recently found to be immunogenic after treatment with several chemotherapeutic agents and oncolytic viruses through the emission of various danger-associated molecular patterns (DAMPs). Extensive studies have revealed that two different types of immunogenic cell death (ICD) inducers, recently classified by their distinct actions in endoplasmic reticulum (ER) stress, can reinitiate immune responses suppressed by the tumor microenvironment. Indeed, recent clinical studies have shown that several immunotherapeutic modalities including therapeutic cancer vaccines and oncolytic viruses, but not conventional chemotherapies, culminate in beneficial outcomes, probably because of their different mechanisms of ICD induction. Furthermore, interests in PCD of cancer cells have shifted from its classical form to novel forms involving autophagic cell death (ACD), programmed necrotic cell death (necroptosis), and pyroptosis, some of which entail immunogenicity after anticancer treatments. In this review, we provide a brief outline of the well-characterized DAMPs such as calreticulin (CRT) exposure, high-mobility group protein B1 (HMGB1), and adenosine triphosphate (ATP) release, which are induced by the morphologically distinct types of cell death. In the latter part, our review focuses on how emerging oncolytic viruses induce different forms of cell death and the combinations of oncolytic virotherapies with further immunomodulation by cyclophosphamide and other immunotherapeutic modalities foster dendritic cell (DC)-mediated induction of antitumor immunity. Accordingly, it is increasingly important to fully understand how and which ICD inducers cause multimodal ICD, which should aid the design of reasonably multifaceted anticancer modalities to maximize ICD-triggered antitumor immunity and eliminate residual or metastasized tumors while sparing autoimmune diseases.

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Section: Open Questionsmentioning

confidence: 99%

Multimodal immunogenic cancer cell death as a consequence of anticancer cytotoxic treatments

2013

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“…Orthotopic cancer models in immunocompetent animals susceptible to the oncolytic virus represent the most reliable and predictive preclinical model for oncolytic virotherapy. 29 An immune response could, in fact, limit viral spread, hence, causing a decrease of cytotoxic effects as it has been shown for adenoviral vectors. 30,31 Besides, a very strong immune response could hypothetically trigger a fatal inflammation leading to death.…”

Section: Discussionmentioning

confidence: 98%

Efficacy of HER2 retargeted herpes simplex virus as therapy for high-grade glioma in immunocompetent mice

et al. 2012

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Replication-competent oncolytic herpes simplex viruses (HSVs) are considered a promising therapeutic approach for treatment of high-grade gliomas (HGGs), which are usually resistant to all the available treatments. We previously demonstrated that R-LM113, a recombinant HSV-1 fully retargeted to the human epidermal growth factor receptor 2 (HER2), is safe and prolongs survival of immunodeficient NOD/SCID mice in an intracranial model of HGG. However, because the treatment is designed to be employed on immunocompetent patients, it is necessary to test whether the host immune system impairs the viral efficacy or triggers a potentially fatal reaction. Here we confirmed the safety of R-LM113 in the immunocompetent mouse strain BALB/c, where it does not trigger encephalitis when intracranially inoculated. Then, we set up a syngeneic HGG model expressing HER2 in adult BALB/c mice and evaluated R-LM113 therapeutic efficacy. We found that R-LM113 leads to a significant improvement in animal survival when administered at the time of tumor inoculation, as well as when injected into an already established tumor. This study suggests that the host immune defenses do not curtail the oncolytic antitumor activity of replication-competent HSV R-LM113, which results effective in counteracting tumor growth.

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“…Oncolytic viruses have promising application in cancer therapy,13 while the clinical applications are restricted by virus‐associated safety issues. [[qv: 5a,14]] Previously, many attempts have been performed to reduce the virus‐associated safety issues by virus modification 15.…”

Section: Discussionmentioning

confidence: 99%

A Vesicular Stomatitis Virus‐Inspired DNA Nanocomplex for Ovarian Cancer Therapy

et al. 2017

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Gene therapy provides a novel method for cancer therapy. This study shows a DNA nanocomplex that is inspired from vesicular stomatitis virus (VSV) for ovarian cancer therapy. This DNA nanocomplex consists of a cationized monomethoxy poly (ethylene glycol)‐poly (d,l‐lactide) (MPEG‐PLA) nanoparticle and a plasmid encoding the matrix protein of vesicular stomatitis virus (VSVMP) that plays a critical role in the VSV‐induced apoptosis of cancer cells. The cationized MPEG‐PLA nanoparticle that is self‐assembled by MPEG‐PLA copolymer and N‐[1‐(2,3‐dioleoyloxy) propyl]‐N,N,N‐trimethylammonium chloride (DOTAP) has low cytotoxicity and high transfection efficiency (>80%). Intraperitoneal administration of the pVSVMP nanocomplex remarkably inhibits the intraperitoneal metastasis of ovarian cancer and does not cause significant systemic toxicity. The apoptosis induction and anti‐angiogenesis are involved in the anticancer mechanism. This work demonstrates a VSV‐inspired DNA nanocomplex that has potential application for the treatment of intraperitoneal metastasis of ovarian cancer.

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Oncolytic virotherapy

Cited by 1,214 publications

References 160 publications

Multimodal immunogenic cancer cell death as a consequence of anticancer cytotoxic treatments

Multimodal immunogenic cancer cell death as a consequence of anticancer cytotoxic treatments

Efficacy of HER2 retargeted herpes simplex virus as therapy for high-grade glioma in immunocompetent mice

A Vesicular Stomatitis Virus‐Inspired DNA Nanocomplex for Ovarian Cancer Therapy

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