In vivo targeting of dendritic cells for activation of cellular immunity using vaccine carriers based on pH-responsive microparticles

Proc Natl Acad Sci U S A. 2005 Dec 20;102(51):18264-8. doi: 10.1073/pnas.0509541102. Epub 2005 Dec 12.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Antibodies, Monoclonal / immunology
  • Cells, Cultured
  • Dendritic Cells / immunology*
  • Endocytosis
  • Female
  • Hydrogen-Ion Concentration
  • Immunity, Cellular / immunology*
  • Lymphocyte Activation / immunology
  • Mice
  • Microspheres*
  • Rats
  • T-Lymphocytes, Cytotoxic / immunology
  • Vaccines / administration & dosage*
  • Vaccines / immunology*

Substances

  • Antibodies, Monoclonal
  • Vaccines