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Nectin-1 expression correlates with the susceptibility of malignant melanoma to oncolytic herpes simplex virus in vitro and in vivo

Schwertner B, Lindner G, Toledo Stauner C, Klapproth E, Magnus C, Rohrhofer A, Gross S, Schuler-Thurner B, Öttl V, Feichtgruber N, Drexler K, Evert K, Krahn MP, Berneburg M, Schmidt B, Schuster P, Haferkamp S (2021)

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Publication Type: Journal article

Publication year: 2021

Journal

Book Volume: 13

Article Number: 3058

Journal Issue: 12

DOI: 10.3390/cancers13123058

Abstract

Talimogene laherparepvec (T-VEC), an oncolytic herpes simplex virus, is approved for intralesional injection of unresectable stage IIIB/IVM1a melanoma. However, it is still unclear which parameter(s) predict treatment response or failure. Our study aimed at characterizing surface receptors Nectin-1 and the herpes virus entry mediator (HVEM) in addition to intracellular molecules cyclic GMP-AMP synthase (cGAS) and stimulator of interferon genes (STING) as potential bio-markers for oncolytic virus treatment. In 20 melanoma cell lines, oncolytic activity of T-VEC was correlated with the expression of Nectin-1 but not HVEM, as evaluated via flow cytometry and immunohistochemistry. Knockout using CRISPR/Cas9 technology confirmed the superior role of Nectin-1 over HVEM for entry and oncolytic activity of T-VEC. Neither cGAS nor STING as evaluated by Western Blot and immunohistochemistry correlated with T-VEC induced oncolysis. The role of these biomarkers was retrospectively analyzed for the response of 35 cutaneous melanoma metastases of 21 patients to intralesional T-VEC injection, with 21 (60.0%) of these lesions respond-ing with complete (n = 16) or partial regression (n = 5). Nectin-1 expression in pretreatment biopsies significantly predicted treatment outcome, while the expression of HVEM, cGAS, and STING was not prognostic. Altogether, Nectin-1 served as biomarker for T-VEC-induced melanoma regression in vitro and in vivo.

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APA:

Schwertner, B., Lindner, G., Toledo Stauner, C., Klapproth, E., Magnus, C., Rohrhofer, A.,... Haferkamp, S. (2021). Nectin-1 expression correlates with the susceptibility of malignant melanoma to oncolytic herpes simplex virus in vitro and in vivo. Cancers, 13(12). https://doi.org/10.3390/cancers13123058

MLA:

Schwertner, Barbara, et al. "Nectin-1 expression correlates with the susceptibility of malignant melanoma to oncolytic herpes simplex virus in vitro and in vivo." Cancers 13.12 (2021).

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