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

doi:10.3390/toxins8060184

Anti-Human Endoglin (hCD105) Immunotoxin-Containing Recombinant Single Chain Ribosome-Inactivating Protein Musarmin 1

Toxins (Basel). 2016 Jun 10;8(6):184. doi: 10.3390/toxins8060184.

Authors

Begoña Barriuso¹, Pilar Antolín², F Javier Arias^{3

4}, Alessandra Girotti⁵, Pilar Jiménez⁶, Manuel Cordoba-Diaz⁷, Damián Cordoba-Diaz⁸, Tomás Girbés⁹

Affiliations

¹ Department of Biochemistry and Molecular Biology, University of Valladolid, 47005 Valladolid, Spain. barmagma@jcyl.es.
² Department of Biochemistry and Molecular Biology, University of Valladolid, 47005 Valladolid, Spain. mantolin@umh.es.
³ Department of Biochemistry and Molecular Biology, University of Valladolid, 47005 Valladolid, Spain. arias@bioforge.uva.es.
⁴ Bioforge, University of Valladolid, Spain and Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), 47002 Valladolid, Spain. arias@bioforge.uva.es.
⁵ Bioforge, University of Valladolid, Spain and Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), 47002 Valladolid, Spain. agirotti@bioforge.uva.es.
⁶ Department of Nutrition and Bromatology, University of Valladolid, 47005 Valladolid, Spain. pilarj@bio.uva.es.
⁷ Department of Pharmacy & Pharmaceutical Technology and University Institute of Industrial Pharmacy (IUFI), Complutense University of Madrid, 28040 Madrid, Spain. mcordoba@farm.ucm.es.
⁸ Department of Pharmacy & Pharmaceutical Technology and University Institute of Industrial Pharmacy (IUFI), Complutense University of Madrid, 28040 Madrid, Spain. damianco@farm.ucm.es.
⁹ Department of Nutrition and Bromatology, University of Valladolid, 47005 Valladolid, Spain. girbes@bio.uva.es.

Abstract

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.

Keywords: 44G4; CD105; anti-endoglin monoclonal antibody; anti-tumor therapy; cancer therapy; endoglin; recombinant musarmin.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cell Line
Cell Survival / drug effects
Endoglin / immunology*
Humans
Immunotoxins / pharmacology*
Mice
N-Glycosyl Hydrolases / pharmacology*

Substances

Endoglin
Immunotoxins
N-Glycosyl Hydrolases
musarmin 1, Muscari armeniacum