RESUMEN
CD8+ T cell-mediated immune response plays a major role in the clearance of virus-infected cells, including human papillomavirus (HPV). The effective treatment of women with normal cytology but persistent high risk-HPV infection or with low-grade intraepithelial lesions could take advantage of novel strategies based on vaccination with viral immunological targets with a wide spectrum of cross-protection. The helicase E1, expressed early during viral replication in HPV infection, is among the most conserved papillomavirus proteins, which makes it a good vaccine candidate. In the present study, we examined E1-specific CD8+ T cell and NK immune responses in a mouse model with α-galactosylceramide (α-GalCer) as an adjuvant. We found that mice immunized with E1 combined with α-GalCer elicited an E1-specific CD8+ T and NK cell cytotoxic responses, which correlated with growth inhibition of grafted melanoma B16-F0 cells expressing E1, both in prophylactic and therapeutic protocols.
Asunto(s)
Vacunas contra el Cáncer/inmunología , Citotoxicidad Inmunológica , Galactosilceramidas/administración & dosificación , Proteínas Oncogénicas Virales/inmunología , Linfocitos T Citotóxicos/inmunología , Adyuvantes Inmunológicos/administración & dosificación , Animales , Femenino , Galactosilceramidas/inmunología , Papillomavirus Humano 18 , Humanos , Células Asesinas Naturales/inmunología , Melanoma Experimental/prevención & control , Melanoma Experimental/terapia , Melanoma Experimental/virología , Ratones , Ratones Endogámicos C57BL , Proteínas Oncogénicas Virales/administración & dosificación , Infecciones por Papillomavirus/inmunología , Infecciones por Papillomavirus/prevención & control , Infecciones por Papillomavirus/terapia , Trasplantes , Células Tumorales Cultivadas/inmunología , VacunaciónRESUMEN
Interferon tau (IFN-τ) is a promising alternative antiviral and immunotherapeutic agent in a wide variety of diseases including infectious, neurodegenerative, autoimmune and cancer due to its low toxicity in comparison with other type I interferon´s. The objective of our study was established the effect of the bovine IFN-τ on human (SiHa) and murine (BMK-16/myc) cells transformed with HPV 16 and evaluates the antitumor effect in a murine tumor model HPV 16 positive. We determine that bovine IFN-τ has antiproliferative effects, pro-apoptotic activity and induces repression of viral E6 and E7 oncogenes (time- and dose-dependent) on human and murine cells transformed with HPV 16 similar to the effects of IFN-ß. However, IFN-τ induces greater antiproliferative effect, apoptosis and repression of both oncogenes in BMK-16/myc cells compared to SiHa cells. The differences were explained by the presence and abundance of the type I interferon receptor (IFNAR) in each cell line. On the other hand, we treated groups of tumor-bearing mice (HPV16 positive) with IFN-τ and showed the inhibition tumor growth effect in vivo. Our finding indicates that bovine IFN-τ may be a good candidate for immunotherapy against cervical cancer.