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.
Highlights
Attacking cancer cells with drugs can be performed either directly by targeting cells or indirectly by destroying the new blood vessels induced by the tumor which each support hundreds of cancer cells
In the present present work, we report proof of the validity of the new IT, containing Recombinant Musarmin 1 (rMU1) as a work, we report proof of the validity of the new IT, containing rMU1 as a toxic moiety toxic moiety linked to an anti-human CD105 monoclonal antibody (44G4), on cultured mouse L929 linked to an anti‐human CD105 monoclonal antibody (44G4), on cultured mouse L929 fibroblasts fibroblasts transfected with the short form of CD105 [22]. rMU1, a recombinant form expressed in transfected with the short form of CD105 [22]. rMU1, a recombinant form expressed in Escherichia coli, Escherichia coli, of musarmin 1 (MU1) present in bulbs of the plant Muscari armeniacum L
The present results open up the possibility of developing fusion proteins carrying the cytotoxic domain of rMU1 and binding domains specific for plasma membrane–inserted CD105
Summary
Attacking cancer cells with drugs can be performed either directly by targeting cells or indirectly by destroying the new blood vessels induced by the tumor which each support hundreds of cancer cells. The latter strategy is known as the antiangiogenic approach to cancer therapy [1]. Recent research has supported the idea that silencing it promotes a significant antitumor effect on murine mammary adenocarcinoma [15]. Targeting endoglin over-expressed in tumor neovasculature has been used for therapeutic. RMU1, a recombinant form expressed in Escherichia coli, Escherichia coli, of musarmin 1 (MU1) present in bulbs of the plant Muscari armeniacum L.
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