Abstract
Tumour growth is characterised by the formation of a fine vessel network or neovasculature which nourishes tumour cells. Two kinds of novel anti-angiogenic therapies are based on the prevention of vessels growth and on the destruction of those vessels already formed. We report here on the design and construction of a novel immunotoxin formed with the non-toxic type II ribosome-inactivating protein ebulin l and the mouse anti-human CD105 monoclonal antibody 44G4. The 44G4-ebulin immunotoxin was formed by covalent linking of both proteins with N-succinimidyl-3- (2-pyridyldithio)propionate (SPDP) and was purified by chromatography on Superdex 200 HiLoad. The analysis of the anti-ribosomal effects in a cell-free translation system indicated that conjugation does not affect the activity of ebulin l. The immunotoxin displays cytotoxicity with nanomolar IC50 values on human CD105+ cells like the mouse fibroblasts L929 cells transfected with the short form of human CD105 and the rat myoblasts L6E9 transfected with the long form of human CD105. In contrast, cells lacking human CD105 were 2-2.5 logs less sensitive to the immunotoxin. Free ebulin displays IC50 values in the range 10-6 M. Since CD105 is being considered as a potential target for the anti-vascular therapy of tumours, the present immunotoxin could be a promising tool for the anticancer therapy, especially due to the very low in vivo toxicity of ebulin l as compared ricin and other toxins used for immunotoxins.
Keywords: ebulin l, endoglin, cd105, anti-endoglin antibody, l929 cells, l6e9 cells, cancer therapy, anti-tumour therapy
Medicinal Chemistry
Title: Cytotoxicity of an Ebulin l-Anti-Human CD105 Immunotoxin on Mouse Fibroblasts (L929) and Rat Myoblasts (L6E9) Cells Expressing Human CD105
Volume: 1 Issue: 1
Author(s): Jorge Benitez, J. Miguel Ferreras, Raquel Munoz, Yolanda Arias, Rosario Iglesias, Manuel Cordoba-Diaz, Rosario del Villar and Tomas Girbes
Affiliation:
Keywords: ebulin l, endoglin, cd105, anti-endoglin antibody, l929 cells, l6e9 cells, cancer therapy, anti-tumour therapy
Abstract: Tumour growth is characterised by the formation of a fine vessel network or neovasculature which nourishes tumour cells. Two kinds of novel anti-angiogenic therapies are based on the prevention of vessels growth and on the destruction of those vessels already formed. We report here on the design and construction of a novel immunotoxin formed with the non-toxic type II ribosome-inactivating protein ebulin l and the mouse anti-human CD105 monoclonal antibody 44G4. The 44G4-ebulin immunotoxin was formed by covalent linking of both proteins with N-succinimidyl-3- (2-pyridyldithio)propionate (SPDP) and was purified by chromatography on Superdex 200 HiLoad. The analysis of the anti-ribosomal effects in a cell-free translation system indicated that conjugation does not affect the activity of ebulin l. The immunotoxin displays cytotoxicity with nanomolar IC50 values on human CD105+ cells like the mouse fibroblasts L929 cells transfected with the short form of human CD105 and the rat myoblasts L6E9 transfected with the long form of human CD105. In contrast, cells lacking human CD105 were 2-2.5 logs less sensitive to the immunotoxin. Free ebulin displays IC50 values in the range 10-6 M. Since CD105 is being considered as a potential target for the anti-vascular therapy of tumours, the present immunotoxin could be a promising tool for the anticancer therapy, especially due to the very low in vivo toxicity of ebulin l as compared ricin and other toxins used for immunotoxins.
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Benitez Jorge, Ferreras Miguel J., Munoz Raquel, Arias Yolanda, Iglesias Rosario, Cordoba-Diaz Manuel, Villar del Rosario and Girbes Tomas, Cytotoxicity of an Ebulin l-Anti-Human CD105 Immunotoxin on Mouse Fibroblasts (L929) and Rat Myoblasts (L6E9) Cells Expressing Human CD105, Medicinal Chemistry 2005; 1 (1) . https://dx.doi.org/10.2174/1573406053402479
DOI https://dx.doi.org/10.2174/1573406053402479 |
Print ISSN 1573-4064 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-6638 |
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