Particulate mediators of the bystander effect linked to suicide and interferon-β transgene expression in melanoma cells
| Autor: | Chiara Fondello, María Florencia Arbe, Lucrecia Agnetti, Liliana M.E. Finocchiaro, Gerardo Claudio Glikin |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Ganciclovir INTERFERON-BETA CIENCIAS MÉDICAS Y DE LA SALUD Genetic enhancement GENE THERAPY Biology Thymidine Kinase 03 medical and health sciences Dogs 0302 clinical medicine THYMIDINE KINASE Interferon In vivo Genetics medicine Bystander effect Animals Humans Simplexvirus Transgenes Melanoma Molecular Biology EXTRACELLULAR VESICLES Bystander Effect Interferon-beta PARTICULATE FACTORS Bioquímica y Biología Molecular Suicide gene medicine.disease BYSTANDER EFFECT Medicina Básica 030104 developmental biology Thymidine kinase 030220 oncology & carcinogenesis Cats Cancer research Molecular Medicine medicine.drug |
| Zdroj: | Gene Therapy. 28:38-55 |
| ISSN: | 1476-5462 0969-7128 |
| Popis: | 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. Fil: Agnetti, Lucrecia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Dr. Ángel Roffo". Unidad de Transferencia Genética; Argentina Fil: Fondello, Chiara. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Dr. Ángel Roffo". Unidad de Transferencia Genética; Argentina Fil: Arbe, María Florencia. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Dr. Ángel Roffo". Unidad de Transferencia Genética; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina Fil: Glikin, Gerardo Claudio. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Dr. Ángel Roffo". Unidad de Transferencia Genética; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina Fil: Finocchiaro, Liliana Maria Elena. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Dr. Ángel Roffo". Unidad de Transferencia Genética; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina |
| Databáze: | OpenAIRE |
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