Enhanced antigen presentation and CTL activity by transduction of mature rather than immature dendritic cells with octaarginine-modified liposomes

Atthachai Homhuan, Kentaro Kogure, Takashi Nakamura, Nilabh Shastri, Hideyoshi Harashima

Research output: Contribution to journalArticlepeer-review

Abstract

To improve uptake and cross-presentation of exogenous antigens (Ag) by dendritic cells (DCs), octaarginine-modified liposomes (R8-Lip) were used as a novel strategy for protein-Ag transduction. Immature DCs endocytose macromolecules efficiently. While mature DCs lose their ability to capture Ag, but have an increased capacity for T-cell activation. Thus Ag-transduction has been performed mostly in immature DCs. In the present study, R8-Lip were efficiently taken up by both immature and mature DCs. DCs transduced after maturation were highly efficient at cross-presentation of Ag and induced higher cytotoxic T-lymphocytes (CTL) activity than were DCs transduced before maturation. The mechanism of Ag presentation involved the escape of R8-Lip from endosomes to cytosol, which require the acidic environment. The Ag released was then processed by a proteasome-dependent pathway. This novel transduction approach is clinically applicable, easy to perform, and has more practical advantages than current protein transduction methods.

Original languageEnglish (US)
Pages (from-to)79-85
Number of pages7
JournalJournal of Controlled Release
Volume136
Issue number1
DOIs
StatePublished - May 21 2009
Externally publishedYes

Keywords

  • Antigen presentation
  • Cytotoxic T lymphocytes
  • Dendritic cells
  • Octaarginine-modified liposomes
  • Protein transduction

ASJC Scopus subject areas

  • Pharmaceutical Science

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