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- Title
Toll-like receptor activation enhances cell-mediated immunity induced by an antibody vaccine targeting human dendritic cells.
- Authors
Ramakrishna, Venky; Vasilakos, John P.; Tario Jr., Joseph D.; Berger, Marc A.; Wallace, Paul K.; Keler, Tibor
- Abstract
Previously, we have successfully targeted the mannose receptor (MR) expressed on monocytederived 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 (hCGβ). Since MRs play a role in bridging innate immunity with adaptive immunity we have explored several tolllike 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-hCGβ-treated autologous DCs when a combination of one or several TLR ligands is used. Specifically, concomitant signaling of DCs via TLR3 with dsRNA (poly I:C) 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.
- Subjects
DENDRITIC cells; ANTIGEN presenting cells; CANCER patients; ANTIGENS; IMMUNOLOGICAL adjuvants; TUMOR antigens; TUMOR markers
- Publication
Journal of Translational Medicine, 2007, Vol 5, p5
- ISSN
1479-5876
- Publication type
Article
- DOI
10.1186/1479-5876-5-5