Gene transfer in dendritic cells, induced by oral DNA vaccination with Salmonella typhimurium, results in protective immunity against a murine fibrosarcoma

摘要: A live attenuated AroA− auxotrophic mutant of Salmonella typhimurium (SL7207) has been used as carrier for the pCMVβ vector that contains β-galactosidase (β-gal) gene under control immediate early promoter Cytomegalovirus (CMV). We tested whether orally administered bacterial could enter and deliver transgene to antigen-presenting cells (APCs) through natural enteric route infection β-gal expression generate a protective response against an aggressive murine fibrosarcoma transduced with (F1.A11) behaves operationally tumor-associated antigen. After three courses, at 15-day intervals, mice developed both cell-mediated systemic humoral responses β-gal. Mice vaccinated harboring pCMVβ, but not plasmid-less carrier, showed resistance challenge F1.A11 cells. These experiments suggest -based DNA immunization allows us specifically target antigen in vivo APCs. To prove is actually expressed by APCs function eukaryotic promoter, green fluorescent protein (GFP) was placed either eukariotic CMV or prokaryotic promoter. Using cytofluorometric analysis, GFP detected only splenocytes receiving results indicate occurs because -mediated transfer Finally, approximately 19% GFP. Among them, F4/80+ macrophages CD11cbright dendritic (DCs) were scored positive expression. Extensive work performed trying optimize way transfect DCs, ex vivo, genes coding relevant antigens. show here, first time, DCs can be directly such induce vaccination tumors. © 1998 The American Society Hematology.