Nectin-1 Expression Correlates with the Susceptibility of Malignant Melanoma to Oncolytic Herpes Simplex Virus In Vitro and In Vivo

Schwertner, B; Lindner, Georg; Stauner, Camila Toledo; Klapproth, Elisa; Magnus, Clara Luzia; Rohrhofer, Anette; Groß, Stefanie; Schuler‐Thurner, Beatrice; Öttl, Veronika; Feichtgruber, Nicole; Drexler, Konstantin; Evert, Katja; Krahn, Michael P.; Berneburg, Mark; Schmidt, Bárbara; Schuster, Philipp; Haferkamp, Sebastian

doi:10.3390/cancers13123058

Cited by 7 publications

(7 citation statements)

References 40 publications

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“…Recently, it was reported that Nectin-1 expression increased the susceptibility of malignant melanoma to an oncolytic herpes simplex virus in vitro and in vivo by promoting the entry of the oncolytic herpes simplex virus and could serve as a biomarker for T-VEC-induced melanoma regression [42]. In our studies, we also demonstrated that BACH1 deficiency could enhance HSV-1mediated antitumor activity.…”

Section: Discussionsupporting

confidence: 74%

Enhancing the HSV-1-mediated antitumor immune response by suppressing Bach1

Pan

Cai

et al. 2022

Cell Mol Immunol

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BACKGROUND:In 2015, herpes simplex virus 1 (HSV-1)-derived talimogene laherparepvec (T-VEC) was the first oncolytic virus approved by the US Food and Drug Administration as a therapeutic agent for cancer treatment. However, its antitumor application is limited to local treatment of melanoma, and there is a lack of understanding of the mechanisms underlying the regulation of HSV-1 replication in cancer cells and the associated antitumor immunity. We hypothesized that increasing the replication capacity of HSV-1 in tumor cells would enhance the antitumor effect of this virus. METHODS: We systematically identified IFN-stimulated genes induced by HSV-1 by performing functional screens and clarified the mechanism by which BACH1 acts against HSV-1. Then, we tested the effect of BACH1 deficiency on immunogenic cell death induced by HSV-1. Furthermore, we investigated the antitumor effect of BACH1 deficiency on HSV-1 in MCA205 and B16 murine tumor models. RESULTS: We identified eight IFN-stimulated genes (ISGs) controlling HSV-1 replication, among which BTB and CNC homology 1 (BACH1) suppressed HSV-1 replication by inhibiting the transcription of ICP4, ICP27, and UL39. Loss of Bach1 function not only increased HSV-1 proliferation but also promoted HSV-1-induced cell apoptosis, HMGB1 secretion, and calreticulin exposure in tumor cells. More importantly, hemin, an FDA-approved drug known to downregulate BACH1, significantly enhanced HSV-1-mediated antitumor activity with increased T lymphocyte infiltration at the tumor site. CONCLUSIONS: Our studies uncovered a novel antiviral activity of BACH1 and provided a new strategy for improving the clinical efficiency of the oncolytic virus HSV-1.

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Section: Discussionsupporting

confidence: 74%

Enhancing the HSV-1-mediated antitumor immune response by suppressing Bach1

Pan

Cai

et al. 2022

Cell Mol Immunol

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“…For MV and HSV, this observation could not be made. In contrast to previously published data for melanoma, 46 PDAC cultures infected with HSV did not release LDH, as shown for eight cultures in Fig. S4 .…”

Section: Resultscontrasting

confidence: 99%

Biomarker screen for efficacy of oncolytic virotherapy in patient-derived pancreatic cancer cultures

Schäfer,

Knol,

Haas

et al. 2024

eBioMedicine

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“…Like measles virus, HSV was engineered into a therapy agent. Studies on different neoplasms-like squamous cell carcinoma, gliomas, melanoma, myeloma and some hematological malignancies-suggest that oncolytic HSV has the potential to cause disease regression and might be considered as a treatment option in the future [73][74][75][76][77].…”

Section: Discussionmentioning

confidence: 99%

Clinical Significance of Nectins in HCC and Other Solid Malignant Tumors: Implications for Prognosis and New Treatment Opportunities—A Systematic Review

Klekowski

Zielińska²,

Hofman

et al. 2023

Cancers

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The nectin family comprises four proteins, nectin-1 to -4, which act as cell adhesion molecules. Nectins have various regulatory functions in the immune system and can be upregulated or decreased in different tumors. The literature research was conducted manually by the authors using the PubMed database by searching articles published before 2023 with the combination of several nectin-related keywords. A total of 43 studies were included in the main section of the review. Nectins-1–3 have different expressions in tumors. Both the loss of expression and overexpression could be negative prognostic factors. Nectin-4 is the best characterized and the most consistently overexpressed in various tumors, which generally correlates with a worse prognosis. New treatments based on targeting nectin-4 are currently being developed. Enfortumab vedotin is a potent antibody–drug conjugate approved for use in therapy against urothelial carcinoma. Few reports focus on hepatocellular carcinoma, which leaves room for further studies comparing the utility of nectins with commonly used markers.

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Nectin-1 Expression Correlates with the Susceptibility of Malignant Melanoma to Oncolytic Herpes Simplex Virus In Vitro and In Vivo

Cited by 7 publications

References 40 publications

Enhancing the HSV-1-mediated antitumor immune response by suppressing Bach1

Enhancing the HSV-1-mediated antitumor immune response by suppressing Bach1

Biomarker screen for efficacy of oncolytic virotherapy in patient-derived pancreatic cancer cultures

Clinical Significance of Nectins in HCC and Other Solid Malignant Tumors: Implications for Prognosis and New Treatment Opportunities—A Systematic Review

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