Anti-Human Endoglin (hCD105) Immunotoxin—Containing Recombinant Single Chain Ribosome-Inactivating Protein Musarmin 1
Begoña Barriuso,
Pilar Antolín,
F. Javier Arias,
Alessandra Girotti,
Pilar Jiménez,
Manuel Cordoba-Diaz,
Damián Cordoba-Diaz,
Tomás Girbés
Affiliations
Begoña Barriuso
Department of Biochemistry and Molecular Biology, University of Valladolid, 47005 Valladolid, Spain
Pilar Antolín
Department of Biochemistry and Molecular Biology, University of Valladolid, 47005 Valladolid, Spain
F. Javier Arias
Department of Biochemistry and Molecular Biology, University of Valladolid, 47005 Valladolid, Spain
Alessandra Girotti
Bioforge, University of Valladolid, Spain and Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), 47002 Valladolid, Spain
Pilar Jiménez
Department of Nutrition and Bromatology, University of Valladolid, 47005 Valladolid, Spain
Manuel Cordoba-Diaz
Department of Pharmacy & Pharmaceutical Technology and University Institute of Industrial Pharmacy (IUFI), Complutense University of Madrid, 28040 Madrid, Spain
Damián Cordoba-Diaz
Department of Pharmacy & Pharmaceutical Technology and University Institute of Industrial Pharmacy (IUFI), Complutense University of Madrid, 28040 Madrid, Spain
Tomás Girbés
Department of Nutrition and Bromatology, University of Valladolid, 47005 Valladolid, Spain
Endoglin (CD105) is an accessory component of the TGF-β receptor complex, which is expressed in a number of tissues and over-expressed in the endothelial cells of tumor neovasculature. Targeting endoglin with immunotoxins containing type 2 ribosome-inactivating proteins has proved an effective tool to reduce blood supply to B16 mice tumor xenografts. We prepared anti-endoglin immunotoxin (IT)—containing recombinant musarmin 1 (single chain ribosome-inactivating proteins) linked to the mouse anti-human CD105 44G4 mouse monoclonal antibody via N-succinimidyl 3-(2-pyridyldithio) propionate (SPDP). The immunotoxin specifically killed L929 fibroblast mouse cells transfected with the short form of human endoglin with IC50 values in the range of 5 × 10−10 to 10−9 M.