RNA-containing adenovirus/polyethylenimine transfer complexes effectively transduce dendritic cells and induce antigen-specific T cell responses

✍ Scribed by Tatjana C. Gust; Sandra S. Diebold; Matt Cotten; Martin Zenke

• Publisher: John Wiley and Sons
• Year: 2004
• Tongue: English
• Weight: 140 KB
• Volume: 6
• Category: Article
• ISSN: 1099-498X
• DOI: 10.1002/jgm.492

✦ Synopsis

Abstract

Background

Dendritic cells (DCs) are the most potent antigen‐presenting cells in initiating primary immune responses. Given the unique properties of DCs, gene‐modified DCs represent a particularly attractive approach for immunotherapy of diseases such as cancer.

Methods

Gene‐modified DCs were obtained by a receptor‐mediated gene delivery system using adenovirus (Ad) particles as ligand and RNA or DNA condensed by polyethylenimine (PEI). In vitro transcribed polyadenylated or non‐polyadenylated RNA was used. RNA‐transduced DCs were generated expressing chicken ovalbumin (OVA) or chimeric constructs thereof, and compared with DNA‐transduced DCs.

Results

Ad/PEI transfection complexes efficiently delivered RNA into DCs. Such RNA‐transduced DCs induced OVA‐specific T cell responses more effectively than DNA‐transduced DCs. Furthermore, DCs transduced with polyadenylated RNA were more potent in stimulating CD4^+^ and CD8^+^ T cell responses than DCs transduced with non‐polyadenylated RNA and this was particularly important for CD4^+^ T cell responses.

Conclusions

Ad/PEI/RNA transfection is an efficient means for generating RNA‐transduced DCs and for stimulating antigen‐specific T cell responses. Polyadenylation of RNA enhances CD8^+^ T cell responses and is essential for CD4^+^ T cell responses. Copyright © 2004 John Wiley & Sons, Ltd.