Intranasal delivery of cationic liposome-protamine complex mRNA vaccine elicits effective anti-tumor immunity.
Cell Immunol
; 354: 104143, 2020 08.
Article
em En
| MEDLINE
| ID: mdl-32563850
ABSTRACT
Immunization with synthetic mRNA encoding tumor-associated antigens is an emerging vaccine strategy for the treatment of cancer. In order to prevent mRNA degradation, promote antigen-presenting cells antigen presentation, and induce an anti-tumor immune response, we investigated the nasal administration of mRNA vaccines with positively charged protamine to concentrate mRNA, form a stable polycation-mRNA complex, and encapsulate the complex with DOTAP/Chol/DSPE-PEG cationic liposomes. Cationic liposome/protamine complex (LPC) showed significantly greater efficiency in uptake of vaccine particles in vitro and stronger capacities to stimulate dendritic cell maturation, which further induced a potent anti-tumor immune response. Intranasal immunization of mice with cationic LPC containing mRNA encoding cytokeratin 19 provoked a strong cellular immune response and slowed tumor growth in an aggressive Lewis lung cancer model. The results of this study provide evidence that cationic LPC can be used as a safe and effective adjuvant and this mRNA formulation provides a basis for anti-cancer vaccination of humans.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Células Dendríticas
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RNA Mensageiro
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Vacinas Anticâncer
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Queratina-19
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Imunoterapia
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Lipossomos
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Neoplasias Pulmonares
Limite:
Animals
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Female
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Humans
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article