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Title: Expression and targeting of human fibroblast activation protein in a human skin/severe combined immunodeficient mouse breast cancer xenograft model.
Austin Authors: Tahtis, Kiki;Lee, Fook-Thean;Wheatley, Jennifer M;Garin-Chesa, Pilar;Park, John E;Smyth, Fiona E;Obata, Yuichi;Stockert, Elisabeth;Hall, Cathrine M;Old, Lloyd J;Rettig, Wolfgang J;Scott, Andrew M 
Affiliation: Tumour Targeting Program, Ludwig Institute for Cancer Research, Melbourne Branch, Austin, Victoria 3084, Australia
Issue Date: 1-Aug-2003
Publication information: Molecular Cancer Therapeutics; 2(8): 729-37
Abstract: Antigens and receptors that are highly expressed on tumor stromal cells, such as fibroblast activation protein (FAP), are attractive targets for antibody-based therapies because the supporting stroma and vessel network is essential for a solid neoplasm to grow beyond a size of 1-2 mm. The in vivo characterization of antibodies targeting human stromal or vessel antigens is hindered by the lack of an appropriate mouse model system because xenografts in standard mouse models express stromal and vessels elements of murine origin. This limitation may be overcome by the development of a human skin/mouse chimeric model, which is established by transplanting human foreskin on to the lateral flank of severe combined immunodeficient mice. The subsequent inoculation of breast carcinoma MCF-7 cells within the dermis of the transplanted human skin resulted in the production of xenografts expressing stromal and vessel elements of human origin. Widespread expression of human FAP-positive reactive stromal fibroblasts within xenografts was seen up to 2 months posttransplantation and postinjection of cells. Human blood vessel antigen expression also persisted at 2 months posttransplantation and postinjection of cells with murine vessels coexisting with the human vascular supply. The model was subsequently used to evaluate the biodistribution properties of an iodine-131-labeled humanized anti-FAP monoclonal antibody (BIBH-7). The results showed high specific targeting of the stromal compartment of the xenograft, indicating that the model provides a useful and novel approach for the in vivo assessment of the immunotherapeutic potential of molecules targeting human stroma and angiogenic systems.
Gov't Doc #: 12939462
Journal: Molecular cancer therapeutics
Type: Journal Article
Subjects: Animals
Antibodies, Monoclonal
Antigens, Neoplasm.analysis.metabolism
Breast Neoplasms
Cell Line, Tumor
Gene Targeting
H-2 Antigens.metabolism
HLA-A Antigens.analysis
HLA-B Antigens.analysis
HLA-C Antigens.analysis.metabolism
Membrane Proteins
Mice, SCID
Models, Animal
Neoplasm Transplantation
Serine Endopeptidases.analysis
Skin Transplantation
Stromal Cells.enzymology
Transplantation, Heterologous
Tumor Markers, Biological.analysis
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