Artículo
Particulate mediators of the bystander effect linked to suicide and interferon-β transgene expression in melanoma cells
Agnetti, Lucrecia
; Fondello, Chiara
; Arbe, María Florencia
; Glikin, Gerardo Claudio
; Finocchiaro, Liliana Maria Elena
Fecha de publicación:
03/2020
Editorial:
Nature Publishing Group
Revista:
Gene Therapy
ISSN:
0969-7128
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
In the context of comparative oncology, melanoma cells derived from companion animal tumors are good models for optimizing and predicting their in vivo response to therapeutic strategies. Here, we report that human, canine, and feline melanoma cells driven to death by bleomycin, interferon-â gene, or herpes simplex virus thymidine kinase/ganciclovir suicide gene (SG) treatment significantly increased their internal granularity. This fact correlated with the release of a heterogeneous collection of nano- and micro-sized granules as revealed by transmission electron microscopy. While killing lipofected cells, the expressed transgenes and their derived products were incorporated into these granules that were isolated by differential centrifugation. These particulate factors (PFs) were able to transfer, in a dose- and time-dependent manner, appreciable levels of therapeutic genes, related proteins, and drugs. Thus, when recipient cells of SG-carrying PFs were exposed to ganciclovir, this prodrug was efficiently activated, eliminating them. These PFs kept the functionality of their cargo, even after being subjected to adverse conditions, such as the presence of DNase, freezing, or heating. Since our in vitro system did not include any of the immune mechanisms that could provide additional antitumor activity, the chemo-gene treatments amplified by these delivery bags of therapeutic agents offer a great clinical potential.
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Articulos(OCA HOUSSAY)
Articulos de OFICINA DE COORDINACION ADMINISTRATIVA HOUSSAY
Articulos de OFICINA DE COORDINACION ADMINISTRATIVA HOUSSAY
Citación
Agnetti, Lucrecia; Fondello, Chiara; Arbe, María Florencia; Glikin, Gerardo Claudio; Finocchiaro, Liliana Maria Elena; Particulate mediators of the bystander effect linked to suicide and interferon-β transgene expression in melanoma cells; Nature Publishing Group; Gene Therapy; 3-2020; 1-18
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