Improving tumor targeting and therapeutic potential of Salmonella VNP20009 by displaying cell surface CEA-specific antibodies.

ABSTRACT: Genetically modified Salmonella typhimurium VNP20009 (VNP) is a useful vehicle for cancer therapy and vaccine development but exhibits limited tumor targeting in vivo. We engineered a novel VNP derivative that expressed carcinoembryonic antigen (CEA)-specific single chain antibody fragments (scFv) on the cell surface to increase tumor-specific targeting. There was significant scFv cell surface display visualized by flow cytometry and confocal microscopy when cells were probed with fluorescently labeled CEA. Atomic force microscopy (AFM) measurements on whole bacteria confirmed binding of unlabeled CEA to the displayed scFv. The modified VNP strain exhibited increased localization in the upper gastrointestinal tract of CEA transgenic mice and accumulated in CEA-expressing tumors. Furthermor

SUBMITTER: Bereta M 

PROVIDER: S-EPMC3690550 | biostudies-literature | 2007 May

REPOSITORIES: biostudies-literature