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
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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