Depletion of autoreactive B-lymphocytes by a recombinant myelin oligodendrocyte glycoprotein-based immunotoxin.
We report the construction of a fusion protein comprising the extracellular domain of myelin oligodendrocyte glycoprotein (MOG) and a truncated version of Pseudomonas aeruginosa exotoxin A (ETA'). The chimeric immunotoxin targeted MOG-reactive B-lymphocytes by binding selectively to the appropriate receptors, leading to internalization and apoptosis of the target cells. The functionality of the immunotoxin was tested on a MOG-sensitive murine hybridoma cell line and ex vivo on freshly isolated splenocytes from transgenic IgH(MOG) mice. These data demonstrate, for the first time, the specific cytotoxicity of a MOG-containing recombinant immunotoxin expressed in bacteria towards MOG-reactive B-lymphocytes.
Nachreiner
Thomas
T
Fraunhofer IME, Department of Pharmaceutical Product Development, Forckenbeckstr. 6, D-52074 Aachen, Germany. thomas.nachreiner@ime.fraunhofer.de
Kampmeier
Florian
F
Thepen
Theo
T
Fischer
Rainer
R
Barth
Stefan
S
Stöcker
Michael
M
D001402:B-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D002461:Cell Line, Transformed; D049109:Cell Proliferation; D002470:Cell Survival; D004306:Dose-Response Relationship, Immunologic; D005434:Flow Cytometry / Q000379:methods; D006801:Humans; D006825:Hybridomas; D008212:Lymphocyte Depletion; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein / Q000235:genetics* / Q000633:toxicity; D063308:Myelin-Oligodendrocyte Glycoprotein; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000633:toxicity*; D014162:Transfection
C571326:MOG protein, human; C571327:Mog protein, mouse; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D011993:Recombinant Fusion Proteins