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Mol Biotechnol ; 61(10): 742-753, 2019 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-31317318

RESUMEN

Breast cancer is a worldwide health problem, and the complexity of the disease, as well as the lack of treatment specificity, generates an urgent need for developing prophylactic and therapeutic measures. Searching for novel epitope-based approaches able to induce tumour immunity, we designed virus-like particles (VLPs) derived from Human parvovirus B19 assembled of chimeric VP2 proteins displaying two epitopes from the insulin-like growth factor-1 receptor (IGF-1R). Here, we present the generation of two chimeric VP2s that retain the stability, solubility and conditions of purification and assembly of the native VP2. We generated versatile chimeric multiepitope anti-cancer vaccine candidates, which prevented and delayed tumour growth when used in a prophylactic scheme of 4 weekly immunizations prior to 4T1 cell inoculation in female BALB/c mice. The presence of specific antibodies against the displayed epitopes suggests their participation in the protective effect; in contrast, no significant proliferative T-cell responses were recorded following stimulation by specific epitopes. The results comprise an approach whereby fusing desired epitopes from cancer to the N-terminus of B19 VP2 protein can generate a library of chimeric VP2-desired epitopes for further assembly in a designed and personalized epitope delivery system.


Asunto(s)
Neoplasias de la Mama/prevención & control , Epítopos/metabolismo , Parvovirus B19 Humano/metabolismo , Receptor IGF Tipo 1/inmunología , Vacunas de Partículas Similares a Virus/administración & dosificación , Animales , Apoptosis , Neoplasias de la Mama/inmunología , Vacunas contra el Cáncer/administración & dosificación , Vacunas contra el Cáncer/inmunología , Proteínas de la Cápside/genética , Proteínas de la Cápside/metabolismo , Línea Celular Tumoral , Supervivencia Celular , Epítopos/genética , Femenino , Humanos , Inmunización , Ratones , Ratones Endogámicos BALB C , Trasplante de Neoplasias , Parvovirus B19 Humano/genética , Resultado del Tratamiento , Vacunas de Partículas Similares a Virus/genética , Vacunas de Partículas Similares a Virus/inmunología
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