Toll-like receptor activation enhances cell-mediated immunity induced by an antibody vaccine targeting human dendritic cells.
J Transl Med
; 5: 5, 2007 Jan 25.
Article
en En
| MEDLINE
| ID: mdl-17254349
ABSTRACT
Previously, we have successfully targeted the mannose receptor (MR) expressed on monocyte-derived dendritic cells (DCs) using a fully human MR-specific antibody, B11, as a vehicle to deliver whole protein tumor antigens such as the human chorionic gonadotropin hormone (hCGbeta). Since MRs play a role in bridging innate immunity with adaptive immunity we have explored several toll-like receptor (TLR)-specific ligands that may synergize with MR targeting and be applicable as adjuvants in the clinic. We demonstrate that antigen-specific helper and cytolytic T cells from both healthy donors and cancer patients were effectively primed with B11-hCGbeta-treated autologous DCs when a combination of one or several TLR ligands is used. Specifically, concomitant signaling of DCs via TLR3 with dsRNA (poly IC) and DC TLR 7/8 with Resiquimod (R-848), respectively, elicited efficient antigen presentation-mediated by MR-targeting. We demonstrate that MR and TLRs contribute towards maturation and activation of DCs by a mechanism that may be driven by a combination of adjuvant and antibody vaccines that specifically deliver antigenic targets to DCs.
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1
Base de datos:
MEDLINE
Asunto principal:
Células Dendríticas
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Vacunas contra el Cáncer
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Receptores Toll-Like
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Inmunidad Celular
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Anticuerpos
Idioma:
En
Revista:
J Transl Med
Año:
2007
Tipo del documento:
Article