Gene gun-mediated skin transfection with FL gene suppresses the growth of murine fibrosarcoma

Aim : Particle-mediated transfection is known as an efficient method of nonviral
gene transfer. Flt3 ligand (FL) is a growth factor for hematopoietic progenitors ; it
promotes the growth of dendritic cells (DC). DCs are powerful antigen-presenting cells
(APCs) and show a remarkable capacity to stimulate antigen-specific T-cell responses.
In this study, we intended to investigate the suppressive effect on tumor growth by gene
gun-mediated transfer of FL in a murine model. Methods : C57BL/6J mice were injected
intradermally with MCA205 cells. DNA (pNGVL-hFLex)-coated gold particles were delivered
to themouse skin surrounding the target tumor. The expression of FL was determined
by RT-PCR. Analyses by immunohistochemistry and fluorescence-activated cell
sorter (FACS) revealed an increase in the number of DC after treatment with FL. Results :
Gene gun-mediated pNGVL-hFLex transfer significantly inhibited the growth of the
MCA205 tumor. FL transfer markedly increased the number of CD11c+ DCs in the tumor
tissue. Further, the FL-transfected mice exhibited a significantly higher number of CD80+
MHC-II cells. Conclusion : We successfully performed FL therapy using an in vivo gene
gun in order to effectively mobilize DCs in situ and induce suppressive immunity.

The journal of medical investigation : http://medical.med.tokushima-u.ac.jp/jmi/index.html