Isolation and characterization of a scFv antibody specific for tumor endothelial marker 1 (TEM1), a new reagent for targeted tumor therapy

• Published in: Cancer letters Vol. 235; no. 2; pp. 298 - 308
• Main Authors: Marty, Cornelia, Langer-Machova, Zuzana, Sigrist, Sandra, Schott, Herbert, Schwendener, Reto A., Ballmer-Hofer, Kurt
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier Ireland Ltd 28-04-2006; Elsevier Limited
• Subjects: Angiogenesis; Antibody Specificity; Antigens, CD; Antigens, Neoplasm; Cancer; Cell Line; Cytarabine - administration & dosage; Cytarabine - analogs & derivatives; Cytidine - administration & dosage; Cytotoxicity; Deoxyribonucleic acid; DNA; Endosialin; Gene expression; Humans; Immunoglobulin Fragments - administration & dosage; Immunoglobulin Fragments - isolation & purification; Liposomes; Membrane Proteins - immunology; Neoplasm Proteins - immunology; Neoplasms - therapy; Peptide Library; Proteins; Recombinant Proteins - administration & dosage; Recombinant Proteins - isolation & purification; Rodents; scFv; Studies; TEM1; Tumor endothelial marker 1; Tumors; Switzerland; Angiogenesis; Tumor endothelial marker 1; TEM1; Liposomes; Endosialin; scFv
• ISSN: 0304-3835; 1872-7980
• DOI: 10.1016/j.canlet.2005.04.029

Tumor endothelial marker 1 (TEM1) is a protein predominantly expressed on the cell surface of endothelial cells in newly developing blood vessels and on tumor cells. It is therefore ideally suited as a target for anti-angiogenic tumor therapy. Using phage display technology a single chain antibody fragment (scFv-CM6) was isolated that specifically binds to the extracellular part of TEM1. Antibody specificity was determined in ELISA, by Western analysis, fluorescence microscopy and flow cytometry performed with TEM1-expressing cells. ScFv-CM6 was further functionalized and coupled to liposomes. Such immunoliposomes loaded with the cytotoxic drug N
4-octadecyl-1-β-
d-arabinofuranosylcytosine-(5′-5′)-3′-C-ethinylcytidine showed increased binding affinity and up to 80% higher cytotoxic activity towards TEM1-expressing IMR-32 tumor cells compared with control liposomes.