title: Single-chain Fv immunoliposomes for the targeting of fibroblast activation protein-expressing tumor stromal cells.
abstract: Tumor stromal cells have gained increasing attention as possible target for cancer therapy. Fibroblast activation protein (FAP) represents a cell surface antigen selectively expressed by reactive tumor stromal fibroblasts of various cancers. Here, we describe anti-FAP immunoliposomes as carrier systems for active targeting of FAP-expressing cells. As targeting ligand we used single-chain Fv (scFv) molecules cross-reacting with human and mouse FAP. These scFv molecules were genetically modified to express an additional cysteine residue at the C-terminus allowing a defined and site-directed conjugation. Coupling to Mal-PEG(2000)-DSPE containing liposomes resulted in sterically stabilized scFv immunoliposomes showing strong and specific binding to FAP-expressing cells. These immunoliposomes were highly stable when incubated under physiological conditions (human plasma, 37 degrees C). In addition, we could show that binding to FAP-expressing cells leads to internalization of intact liposomes into the endosomal compartment. Thus, these anti-FAP scFv immunoliposomes should be suitable for target cell-specific delivery and uptake of encapsulated drugs.
authors.affiliation: Institut für Zellbiologie und Immunologie, Universität Stuttgart, Stuttgart, Germany.
authors.forename: Patrick
authors.initials: P
authors.lastname: Baum
authors.forename: Dafne
authors.initials: D
authors.lastname: Müller
authors.forename: Ronny
authors.initials: R
authors.lastname: Rüger
authors.forename: Roland E
authors.initials: RE
authors.lastname: Kontermann
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D045744:Cell Line, Tumor; D003429:Cross Reactions; D004337:Drug Carriers; D004355:Drug Stability; D010450:Endopeptidases; D011992:Endosomes / Q000378:metabolism; D018093:Gelatinases; D006801:Humans; D007128:Immunoglobulin Fragments / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D007135:Immunoglobulin Variable Region / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D008081:Liposomes / Q000737:chemistry*; D008565:Membrane Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D010714:Phosphatidylethanolamines; D011092:Polyethylene Glycols; D012697:Serine Endopeptidases / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D017154:Stromal Cells / Q000378:metabolism*; D000099167:Fibroblast Activation Protein Alpha
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D004337:Drug Carriers; D010450:Endopeptidases; D018093:Gelatinases; D007128:Immunoglobulin Fragments; D007135:Immunoglobulin Variable Region; D008081:Liposomes; D008565:Membrane Proteins; D010714:Phosphatidylethanolamines; D011092:Polyethylene Glycols; D012697:Serine Endopeptidases; D000099167:Fibroblast Activation Protein Alpha; C055966:immunoglobulin Fv; C038089:1,2-distearoylphosphatidylethanolamine