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

Abstract

Aim: Particle-mediated transfection is known as an efficient method of non-viral 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 the mouse 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.