Co-delivery of nucleoside-modified mRNA and TLR agonists for cancer immunotherapy: Restoring the immunogenicity of immunosilent mRNA.
J Control Release
; 266: 287-300, 2017 Nov 28.
Article
em En
| MEDLINE
| ID: mdl-28987878
ABSTRACT
This study reports on the design of mRNA and adjuvant-loaded lipid nanoparticles for therapeutic cancer vaccination. The use of nucleoside-modified mRNA has previously been shown to improve the translational capacity and safety of mRNA-therapeutics, as it prevents the induction of type I interferons (IFNs). However, type I IFNs were identified as the key molecules that trigger the activation of antigen presenting cells, and as such drive T cell immunity. We demonstrate that nucleoside-modified mRNA can be co-delivered with the clinically approved TLR agonist monophosphoryl lipid A (MPLA). As such, we simultaneously allow high antigen expression in vivo while substituting the type I IFN response by a more controllable adjuvant. This strategy shows promise to induce effective antigen-specific T cell immunity and may be useful to enhance the safety of mRNA vaccines.
Palavras-chave
5-Methylcytidine (PubChem CID: 92918); Adjuvant; CFSE (PubChem CID: 16211581); Cholesterol (PubChem CID: 5997); DOPE (PubChem CID: 9546757); DOTAP (PubChem CID: 6437371); Dendritic cell; Lipid nanoparticle; MPLA; MPLA (PubChem CID: 5043498); Pseudouridine (PubChem CID: 57369533); SIINFEKL (PubChem CID: 71311993); Type I interferon; mRNA vaccination
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
RNA Mensageiro
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Citidina
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Receptores Toll-Like
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Lipídeo A
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Neoplasias
Limite:
Animals
Idioma:
En
Revista:
J Control Release
Ano de publicação:
2017
Tipo de documento:
Article