In vivo targeting of dendritic cells for activation of cellular immunity using vaccine carriers based on pH-responsive microparticles.
Activating the immune system to trigger a specific response is a major challenge in vaccine development. In particular, activating sufficient cytotoxic T lymphocyte-mediated cellular immunity, which is crucial for the treatment of many diseases including cancer and AIDS, has proven to be especially challenging. In this study, antigens were encapsulated in acid-degradable polymeric particle carriers to cascade cytotoxic T lymphocyte activation. To target dendritic cells, the most potent antigen-presenting cells, the particle carriers, were further conjugated with monoclonal antibodies. A series of ex vivo and in vivo studies have shown increased receptor-mediated uptake of antibody-conjugated particles by dendritic cells as well as migration of particle-carrying dendritic cells to lymph nodes and stimulation of naïve T cells leading to enhanced cellular immune response as confirmed by specific cell lysis and IFN-gamma secretion.
Kwon
Young Jik
YJ
Department of Chemistry, University of California, Berkeley, CA 94720, USA.
James
Edward
E
Shastri
Nilabh
N
Fréchet
Jean M J
JM
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology*; D004705:Endocytosis; D005260:Female; D006863:Hydrogen-Ion Concentration; D007111:Immunity, Cellular / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008863:Microspheres; D051381:Rats; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014612:Vaccines / Q000008:administration & dosage* / Q000276:immunology*
D000911:Antibodies, Monoclonal; D014612:Vaccines