Targeting a marker of the tumour neovasculature using a novel anti-human CD105-immunotoxin containing the non-toxic type 2 ribosome-inactivating protein nigrin b.
Targeting tumour neovasculature using antibodies to the endothelial receptor CD105 (endoglin), is a potentially useful approach for anti-tumour therapy. We report on the preparation and the cytotoxicity of a novel immunotoxin consisting in the non-toxic type 2 ribosome-inactivating protein (RIP) nigrin b linked to the monoclonal anti-human CD105 (hCD105) antibody 44G4. The immunotoxin kills specifically mouse fibroblasts expressing the biomarker CD105 (L929-hCD105+ cells) with an IC(50) value of 6x10(-10)M while nigrin b does it at 2.4x10(-7)M. Immunofluorescence analysis indicated that the immunotoxin accumulates in a perinuclear region. In contrast, 44G4 showed a specific localization on the cell surface.
Muñoz
Raquel
R
Departamento de Bioquímica y Biología Molecular, Facultad de Ciencias, Universidad de Valladolid, E-47005 Valladolid, Spain.
Arias
Yolanda
Y
Ferreras
José M
JM
Rojo
María A
MA
Gayoso
Manuel J
MJ
Nocito
Mercedes
M
Benitez
Jorge
J
Jiménez
Pilar
P
Bernabéu
Carmelo
C
Girbés
Tomas
T
D000818:Animals; D015703:Antigens, CD / Q000276:immunology; D014408:Biomarkers, Tumor / Q000276:immunology*; D002470:Cell Survival; D002478:Cells, Cultured; D000071063:Endoglin; D005260:Female; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D000922:Immunotoxins / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009699:N-Glycosyl Hydrolases / Q000494:pharmacology*; D009389:Neovascularization, Pathologic / Q000188:drug therapy* / Q000378:metabolism; D010940:Plant Proteins / Q000494:pharmacology*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology*; D011956:Receptors, Cell Surface / Q000276:immunology; D054790:Ribosome Inactivating Proteins, Type 2; D012270:Ribosomes / Q000187:drug effects / Q000378:metabolism; D014471:Umbilical Veins / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
D015703:Antigens, CD; D014408:Biomarkers, Tumor; C064206:ENG protein, human; D000071063:Endoglin; D000922:Immunotoxins; D010940:Plant Proteins; D011500:Protein Synthesis Inhibitors; D011956:Receptors, Cell Surface; D054790:Ribosome Inactivating Proteins, Type 2; D009699:N-Glycosyl Hydrolases