Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 1 de 1
Filtrar
Mais filtros








Base de dados
Intervalo de ano de publicação
1.
BMC Cancer ; 19(1): 540, 2019 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-31170937

RESUMO

BACKGROUND: Despite considerable efforts at developing therapeutic vaccines for cancer, clinical translation of preclinical successes has been challenging, largely due to the difficulty of inducing strong and sustained cytotoxic T lymphocyte (CTL) responses in patients. Several peptide-based cancer vaccines have failed to show sustainable tumor regression in the clinic, possibly because of a lack of optimization of both the adjuvant and antigen components of the preparations. Here, we aimed to develop and optimize a vaccine format utilizing a synthetic long peptide (SLP) containing the human papilloma virus 16 (HPV16) E7 antigen, with a centrally located defined MHC class I epitope, and evaluate its immunogenicity and efficacy in combination with various adjuvant formulations. METHODS: E731-73 SLP was tested alone or in combination with toll-like receptor (TLR)3, TLR4, TLR7/8 and TLR9 agonists and formulated in oil-in-water (o/w) or water-in-oil (w/o) emulsions to determine a vaccine format inducing a robust CD8 T cell response in murine models. Once a lead vaccine format was determined, we examined its ability to inhibit tumor growth in the murine TC-1 model that expresses HPV16 E7 antigen. RESULTS: We identified the TLR9 agonist CpG formulated in a squalene-based o/w emulsion as the most potent adjuvant, inducing the expansion of multifunctional antigen specific CD8 T cells with cytolytic potential. We also demonstrated that SLP E731-73 + CpG + o/w emulsion vaccine can provide prophylactic and more importantly, therapeutic benefit in the TC-1 murine tumor model. CONCLUSIONS: Our results demonstrate that the novel vaccine format E7 SLP + CpG delivered in an o/w emulsion holds potential for the promotion of strong CTL responses and tumor eradication and encourages further development of peptide/adjuvant vaccines in cancer immunotherapy strategies.


Assuntos
Vacinas Anticâncer/imunologia , Ilhas de CpG/imunologia , Emulsões/química , Proteínas E7 de Papillomavirus/imunologia , Vacinas contra Papillomavirus/imunologia , Linfócitos T Citotóxicos/imunologia , Vacinação/métodos , Vacinas de Subunidades Antigênicas/imunologia , Adjuvantes Imunológicos , Animais , Linhagem Celular Tumoral , Modelos Animais de Doenças , Epitopos/imunologia , Feminino , Antígenos de Histocompatibilidade Classe I/imunologia , Memória Imunológica , Camundongos , Camundongos Endogâmicos C57BL , Óleos/química , Proteínas E7 de Papillomavirus/síntese química , Receptor Toll-Like 9/agonistas , Receptor Toll-Like 9/imunologia , Carga Tumoral , Vacinas Sintéticas/imunologia , Água/química
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA