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Mol Biotechnol ; 61(10): 742-753, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31317318

RESUMO

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.


Assuntos
Neoplasias da Mama/prevenção & controle , Epitopos/metabolismo , Parvovirus B19 Humano/metabolismo , Receptor IGF Tipo 1/imunologia , Vacinas de Partículas Semelhantes a Vírus/administração & dosagem , Animais , Apoptose , Neoplasias da Mama/imunologia , Vacinas Anticâncer/administração & dosagem , Vacinas Anticâncer/imunologia , Proteínas do Capsídeo/genética , Proteínas do Capsídeo/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular , Epitopos/genética , Feminino , Humanos , Imunização , Camundongos , Camundongos Endogâmicos BALB C , Transplante de Neoplasias , Parvovirus B19 Humano/genética , Resultado do Tratamento , Vacinas de Partículas Semelhantes a Vírus/genética , Vacinas de Partículas Semelhantes a Vírus/imunologia
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