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

Young Jik Kwon, Edward James, Nilabh Shastri, Jean Frechet*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

155 Scopus citations

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-γ secretion.

Original languageEnglish (US)
Pages (from-to)18264-18268
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume102
Issue number51
DOIs
StatePublished - Dec 20 2005

Keywords

  • Acid-degradable particle
  • Drug delivery
  • Targeted vaccine

ASJC Scopus subject areas

  • General

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