Submitted August 28, 2008
Accepted January 5, 2009
Antigen mRNA-transfected, allogeneic fibroblasts loaded with NKT cell ligand confer antitumor immunity
Shin-ichiro Fujii*, Akira Goto, and Kanako Shimizu
Research Unit for Cellular Immunotherapy, The Institute of Physical and Chemical Research (RIKEN), Research Center for Allergy and Immunology, Yokohama, Kanagawa, Japan
Research Unit for Therapeutic Model, The Institute of Physical and Chemical Research (RIKEN), Research Center for Allergy and Immunology, Yokohama, Kanagawa, Japan
* Corresponding author; email: fujiis{at}rcai.riken.jp.
The maturation of dendritic cells (DCs) in situ by danger signals plays a central role in linking innate and adaptive immunity. We previously demonstrated that the activation of invariant (i)NKT cells by administration of 
-galactosylceramide (-GalCer)-loaded tumor cells can act as a cellular adjuvant through the DC maturation. In the current study, we used allogeneic fibroblast cells loaded with -GalCer and transfected with antigen-encoding mRNA, thus combining the adjuvant effects of iNKT cell activation with delivery of antigen to DCs in vivo. We found that these cells produce antigen protein and activate NK and iNKT cells. When injected into MHC mismatched mice, they elicited antigen-specific T cell responses and provided tumor protection, suggesting that these immune responses depend on host DCs. Also, antigen expressing fibroblasts loaded with -GalCer lead to a more potent T cell response than those expressing NK cell ligands. Thus, glycolipid-loaded, mRNA-transfected allogeneic fibroblasts act as cellular vectors to provide iNKT cell activation, leading to DC maturation and T cell immunity. By harnessing the innate immune system and generating an adaptive immune response to a variety of antigens, this unique tool could prove clinically beneficial in the development of immunotherapies against malignant and infectious diseases.
