Immunogenic cell death by oncolytic herpes simplex virus type 1 in squamous cell carcinoma cells

Takasu, Akinori; Masui, Atsushi; Hamada, Mareomi; Imai, Tomoaki; Iwai, Shinichi; Yura, Yoshiaki

doi:10.1038/cgt.2016.8

Cited by 57 publications

(69 citation statements)

References 47 publications

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“…Previous reports have suggested that cells infected with HSV-1 can release byproducts that kill uninfected neighboring cells [22, 23]. We wondered if such a paracrine signal might cause uninfected cells to be more sensitive to alisertib cytotoxicity, contributing to the synergy.…”

Section: Resultsmentioning

confidence: 94%

“…Stanziale and colleagues noted that virus infection increased apoptosis in uninfected cells and limited virus spread, which was reversed with an inhibitor of apoptosis [22]. Takasu et al noted oHSV infection induced a so-called immunogenic cell death with secretion of damage associated molecular patterns ATP and HMGB1, and that intratumoral injection of supernatants from infected cells slowed tumor growth [23]. Although the exact nature of molecules that mediate the bystander effect are not known, it is possible this phenomenon will sensitize cells not only to alisertib but also to other targeted or cytotoxic drugs.…”

Section: Discussionmentioning

confidence: 99%

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Aurora A kinase inhibition enhances oncolytic herpes virotherapy through cytotoxic synergy and innate cellular immune modulation

et al. 2017

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Malignant peripheral nerve sheath tumor (MPNST) and neuroblastoma models respond to the investigational small molecule Aurora A kinase inhibitor, alisertib. We previously reported that MPNST and neuroblastomas are also susceptible to oncolytic herpes virus (oHSV) therapy. Herein, we show that combination of alisertib and HSV1716, a virus derived from HSV-1 and attenuated by deletion of RL1, exhibits significantly increased antitumor efficacy compared to either monotherapy. Alisertib and HSV1716 reduced tumor growth and increased survival in two xenograft models of MPNST and neuroblastoma. We found the enhanced antitumor effect was due to multiple mechanisms that likely each contribute to the combination effect. First, oncolytic herpes virus increased the sensitivity of uninfected cells to alisertib cytotoxicity, a process we term virus-induced therapeutic adjuvant (VITA). Second, alisertib increased peak virus production and slowed virus clearance from tumors, both likely a consequence of it preventing virus-mediated increase of intratumoral NK cells. We also found that alisertib inhibited virus-induced accumulation of intratumoral myeloid derived suppressor cells, which normally are protumorigenic. Our data suggest that clinical trials of the combination of oHSV and alisertib are warranted in patients with neuroblastoma or MPNST.

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Section: Resultsmentioning

confidence: 94%

Section: Discussionmentioning

confidence: 99%

Aurora A kinase inhibition enhances oncolytic herpes virotherapy through cytotoxic synergy and innate cellular immune modulation

et al. 2017

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“…However, a number of other OVs may also induce bona fide ICD, as they indeed serve to prime/induce adaptive antitumor immunity in vivo . The list is quite long and includes oncolytic adenovirus (46), influenza virus (47), HSV (25, 48, 49), measles virus (MeV) (50), NDV (51), VSV (5), and Sendai virus (52). However, we wish to emphasize that significantly more investigations will be required to validate such conjecture.…”

Section: Current Strategies In Oncolytic Immunotherapymentioning

confidence: 99%

Oncolytic Immunotherapy: Conceptual Evolution, Current Strategies, and Future Perspectives

et al. 2017

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The concept of oncolytic virus (OV)-mediated cancer therapy has been shifted from an operational virotherapy paradigm to an immunotherapy. OVs often induce immunogenic cell death (ICD) of cancer cells, and they may interact directly with immune cells as well to prime antitumor immunity. We and others have developed a number of strategies to further stimulate antitumor immunity and to productively modulate the tumor microenvironment (TME) for potent and sustained antitumor immune cell activity. First, OVs have been engineered or combined with other ICD inducers to promote more effective T cell cross-priming, and in many cases, the breaking of functional immune tolerance. Second, OVs may be armed to express Th1-stimulatory cytokines/chemokines or costimulators to recruit and sustain the potent antitumor immunity into the TME to focus their therapeutic activity within the sites of disease. Third, combinations of OV with immunomodulatory drugs or antibodies that recondition the TME have proven to be highly promising in early studies. Fourth, combinations of OVs with other immunotherapeutic regimens (such as prime-boost cancer vaccines, CAR T cells; armed with bispecific T-cell engagers) have also yielded promising preliminary findings. Finally, OVs have been combined with immune checkpoint blockade, with robust antitumor efficacy being observed in pilot evaluations. Despite some expected hurdles for the rapid translation of OV-based state-of-the-art protocols, we believe that a cohort of these novel approaches will join the repertoire of standard cancer treatment options in the near future.

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“…Furthermore, cell death with immunogenic potential, i.e. , immunogenic cell death, was also demonstrated in RH2-infected SCC cells [47].…”

Section: Antitumor Immunitymentioning

confidence: 90%

Presage of oncolytic virotherapy for oral cancer with herpes simplex virus

Yura

2017

Japanese Dental Science Review

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SummaryA virus is a pathogenic organism that causes a number of infectious diseases in humans. The oral cavity is the site at which viruses enter and are excreted from the human body. Herpes simplex virus type 1 (HSV-1) produces the primary infectious disease, gingivostomatitis, and recurrent disease, labial herpes. HSV-1 is one of the most extensively investigated viruses used for cancer therapy. In principle, HSV-1 infects epithelial cells and neuronal cells and exhibits cytotoxicity due to its cytopathic effects on these cells. If the replication of the virus occurs in tumor cells, but not normal cells, the virus may be used as an antitumor agent. Therefore, HSV-1 genes have been modified by genetic engineering, and in vitro and in vivo studies with the oncolytic virus have demonstrated its efficiency against head and neck cancer including oral cancer. The oncolytic abilities of other viruses such as adenovirus and reovirus have also been demonstrated. In clinical trials, HSV-1 is the top runner and is now available for the treatment of patients with advanced melanoma. Thus, melanoma in the oral cavity is the target of oncolytic HSV-1. Oncolytic virotherapy is a hopeful and realistic modality for the treatment of oral cancer.

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Immunogenic cell death by oncolytic herpes simplex virus type 1 in squamous cell carcinoma cells

Cited by 57 publications

References 47 publications

Aurora A kinase inhibition enhances oncolytic herpes virotherapy through cytotoxic synergy and innate cellular immune modulation

Aurora A kinase inhibition enhances oncolytic herpes virotherapy through cytotoxic synergy and innate cellular immune modulation

Oncolytic Immunotherapy: Conceptual Evolution, Current Strategies, and Future Perspectives

Presage of oncolytic virotherapy for oral cancer with herpes simplex virus

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