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

T-VEC herpes simplex virus malignant melanoma nectin-1 oncolytic

Journal

Cancers
ISSN: 2072-6694
Titre abrégé: Cancers (Basel)
Pays: Switzerland
ID NLM: 101526829

Informations de publication

Date de publication:
19 Jun 2021
Historique:
received: 28 05 2021
revised: 15 06 2021
accepted: 16 06 2021
entrez: 2 7 2021
pubmed: 3 7 2021
medline: 3 7 2021
Statut: epublish

Résumé

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 responding with complete (

Identifiants

pubmed: 34205379
pii: cancers13123058
doi: 10.3390/cancers13123058
pmc: PMC8234279
pii:
doi:

Types de publication

Journal Article

Langues

eng

Subventions

Organisme : Deutsche Forschungsgemeinschaft
ID : DFG HA 8481/1-1

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Auteurs

Barbara Schwertner (B)

Department of Dermatology, University Hospital Regensburg, 93053 Regensburg, Germany.

Georg Lindner (G)

Institute of Medical Microbiology and Hygiene, University of Regensburg, 93053 Regensburg, Germany.

Camila Toledo Stauner (C)

Department of Dermatology, University Hospital Regensburg, 93053 Regensburg, Germany.

Elisa Klapproth (E)

Institute of Medical Microbiology and Hygiene, University of Regensburg, 93053 Regensburg, Germany.

Clara Magnus (C)

Institute of Medical Microbiology and Hygiene, University of Regensburg, 93053 Regensburg, Germany.

Anette Rohrhofer (A)

Institute of Clinical Microbiology and Hygiene, University Hospital Regensburg, 93053 Regensburg, Germany.

Stefanie Gross (S)

Department of Dermatology, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, 91054 Erlangen, Germany.

Beatrice Schuler-Thurner (B)

Department of Dermatology, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, 91054 Erlangen, Germany.

Veronika Öttl (V)

Institute of Medical Microbiology and Hygiene, University of Regensburg, 93053 Regensburg, Germany.

Nicole Feichtgruber (N)

Institute of Medical Microbiology and Hygiene, University of Regensburg, 93053 Regensburg, Germany.

Konstantin Drexler (K)

Department of Dermatology, University Hospital Regensburg, 93053 Regensburg, Germany.

Katja Evert (K)

Institute of Pathology, University of Regensburg, 93053 Regensburg, Germany.

Michael P Krahn (MP)

Medical Cell Biology, Internal Medicine D, University Hospital Münster, 48149 Münster, Germany.

Mark Berneburg (M)

Department of Dermatology, University Hospital Regensburg, 93053 Regensburg, Germany.

Barbara Schmidt (B)

Institute of Medical Microbiology and Hygiene, University of Regensburg, 93053 Regensburg, Germany.
Institute of Clinical Microbiology and Hygiene, University Hospital Regensburg, 93053 Regensburg, Germany.

Philipp Schuster (P)

Institute of Medical Microbiology and Hygiene, University of Regensburg, 93053 Regensburg, Germany.

Sebastian Haferkamp (S)

Department of Dermatology, University Hospital Regensburg, 93053 Regensburg, Germany.

Classifications MeSH