RNA as performance-enhancers for dendritic cells.
BACKGROUND
Although studies have demonstrated that antigen-loaded dendritic cells (DC) elicit antigen-specific immune responses, the clinical benefit from DC-based cancer immunotherapy remains low. RNA, in the form of mRNA, has not only been used as a source of antigen but more recently as a way to stimulate DC to produce immunostimulatory molecules. As siRNA it has allowed researchers to modify DC to produce a favorable cytokine profile or to present antigen that may generate the desired immune response.


METHODS
When loading DC with RNA that encodes immunostimulatory protein, rather than a source of antigen, optimal translation and efficient transfection into DC are critical. Studies addressing these issues and the functional consequences of modulating DC function are reviewed.


RESULTS
RNA can be used to load DC with antigen and to encode proteins that will enhance the immune response. Co-transfection with multiple mRNAs or mRNA plus siRNA can significantly improve vaccine efficacy.


CONCLUSIONS
One conclusion from Phase I clinical trials with DC loaded with tumor antigen is that tumor-specific induction of immune responses is not sufficient to destroy pre-established tumors. The advantage of transfection with mRNA is the ability to load DC with antigen-encoding mRNA and immunostimulatory protein-encoding mRNA to achieve the desired clinical response.
Duke University Medical Center, Department of Surgery, Box 103035, Durham, NC 27710, USA.
David
D
Boczkowski
Smita
S
Nair
D000941:Antigens / Q000276:immunology; D002465:Cell Movement; D017321:Clinical Trials, Phase I as Topic; D003713:Dendritic Cells / Q000276:immunology*; D006801:Humans; D014176:Protein Biosynthesis; D012313:RNA / Q000008:administration & dosage* / Q000235:genetics; D014162:Transfection
D000941:Antigens; D012313:RNA