Transfection of RNA encoding tumor antigens following maturation of dendritic cells leads to prolonged presentation of antigen and the generation of high-affinity tumor-reactive cytotoxic T lymphocytes.

Published

Journal Article

Common tumor vaccination strategies utilizing peptide-pulsed dendritic cells (DC) are limited to targeting antigens with known epitopes in patients expressing a defined restricting allele and can result in the preferential induction of low-avidity T cells that fail to recognize tumor cells. The use of dendritic cells transfected with RNA encoding tumor antigen offers the prospect of antigen-specific immunization without requiring prior knowledge of the immunogenic epitope or restricting allele, since epitopes from the translated protein are processed by the endogenous antigen-presentation machinery. However, its use in vaccine studies has been limited by low RNA transfection efficiency and the use of immature DC as recipient cells. In this study, we report an RNA transfection strategy that routinely achieves expression in 40-50% of mature DC, which are better stimulator cells. Such RNA-transfected mature DC exhibited a prolonged duration of presentation of immunogenic epitopes compared to peptide-pulsed DC, induced greater frequencies of tumor antigen-specific CTL, and generated a CTL population that exhibited higher target avidity and increased tumor lytic capacity. These studies provide compelling in vitro data supporting the evaluation of RNA-transfected mature DC in vaccination protocols as a means to overcome several obstacles to generating anti-tumor responses in vivo.

Full Text

Duke Authors

Cited Authors

  • Liao, X; Li, Y; Bonini, C; Nair, S; Gilboa, E; Greenberg, PD; Yee, C

Published Date

  • May 2004

Published In

Volume / Issue

  • 9 / 5

Start / End Page

  • 757 - 764

PubMed ID

  • 15120337

Pubmed Central ID

  • 15120337

International Standard Serial Number (ISSN)

  • 1525-0016

Digital Object Identifier (DOI)

  • 10.1016/j.ymthe.2004.02.011

Language

  • eng

Conference Location

  • United States