title: Novel antibody probes for the characterization of endosialin/TEM-1.
abstract: Endosialin (Tumor Endothelial Marker-1 (TEM-1), CD248) is primarily expressed on pericytes of tumor-associated microvasculature, tumor-associated stromal cells and directly on tumors of mesenchymal origin, including sarcoma and melanoma. While the function of endosialin/TEM-1 is incompletely understood, studies have suggested a role in supporting tumor growth and invasion thus making it an attractive therapeutic target. In an effort to further understand its role in cancer, we previously developed a humanized anti-endosialin/TEM-1 monoclonal antibody (mAb), called ontuxizumab (MORAb-004) for testing in preclinical and clinical studies. We herein report on the generation of an extensive panel of recombinant endosialin/TEM-1 protein extracellular domain (ECD) fragments and novel mAbs against ECD motifs. The domain-specific epitopes were mapped against ECD sub-domains to identify those that can detect distinct structural motifs and can be potentially formatted as probes suitable for diagnostic and functional studies. A number of mAbS were shown to cross-react with the murine and human protein, potentially allowing their use in human animal models and corresponding clinical trials. In addition, pairing of several mAbs supported their use in immunoassays that can detect soluble endosialin/TEM-1 (sEND) in the serum of healthy subjects and cancer patients.
authors: Morphotek, Inc., Exton, PA, USA.
authors: Daniel J
authors: DJ
authors: O'Shannessy
authors: Morphotek, Inc., Exton, PA, USA.
authors: Michael F
authors: MF
authors: Smith
authors: Morphotek, Inc., Exton, PA, USA.
authors: Elizabeth B
authors: EB
authors: Somers
authors: Morphotek, Inc., Exton, PA, USA.
authors: Stephen M
authors: SM
authors: Jackson
authors: Morphotek, Inc., Exton, PA, USA.
authors: Earl
authors: E
authors: Albone
authors: Morphotek, Inc., Exton, PA, USA.
authors: Brian
authors: B
authors: Tomkowicz
authors: Morphotek, Inc., Exton, PA, USA.
authors: Xin
authors: X
authors: Cheng
authors: Morphotek, Inc., Exton, PA, USA.
authors: Young
authors: Y
authors: Park
authors: Morphotek, Inc., Exton, PA, USA.
authors: Danielle
authors: D
authors: Fernando
authors: Morphotek, Inc., Exton, PA, USA.
authors: Andrew
authors: A
authors: Milinichik
authors: Morphotek, Inc., Exton, PA, USA.
authors: Brad
authors: B
authors: Kline
authors: PhenoPath, Seattle, WA, USA.
authors: Regan
authors: R
authors: Fulton
authors: Meso Scale Discovery, Rockville, MD, USA.
authors: Pankaj
authors: P
authors: Oberoi
authors: Morphotek, Inc., Exton, PA, USA.
authors: Nicholas C
authors: NC
authors: Nicolaides
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000918:Antibody Specificity / Q000276:immunology; D015703:Antigens, CD / Q000097:blood / Q000235:genetics / Q000276:immunology*; D000951:Antigens, Neoplasm / Q000097:blood / Q000235:genetics / Q000276:immunology*; D001665:Binding Sites / Q000235:genetics / Q000276:immunology; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D003429:Cross Reactions / Q000276:immunology; D000939:Epitopes / Q000276:immunology*; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D009369:Neoplasms / Q000097:blood / Q000276:immunology / Q000378:metabolism; D011917:Rats, Inbred Lew; D011994:Recombinant Proteins / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000951:Antigens, Neoplasm; C078203:CD248 protein, human; D000939:Epitopes; D011994:Recombinant Proteins
keywords: CD248; TEM-1; endosialin; ontuxizumab; sEND; tumor microenvironment