title: A CSPG4-specific immunotoxin kills rhabdomyosarcoma cells and binds to primary tumor tissues.
abstract: The treatment of rhabdomyosarcoma (RMS) remains challenging, with metastatic and alveolar RMS offering a particularly poor prognosis. Therefore, the identification and evaluation of novel antigens, which are suitable targets for immunotherapy, is one attractive possibility to improve the treatment of this disease. Here we show that chondroitin sulfate proteoglycan 4 (CSPG4) is expressed on RMS cell lines and RMS patient material. We evaluated the immunotoxin (IT) αMCSP-ETA', which specifically recognizes CSPG4 on the RMS cell lines RD, FL-OH1, TE-671 and Rh30. It is internalized rapidly, induces apoptosis and thus kills RMS cells selectively. We also demonstrate the specific binding of this IT to RMS primary tumor material from three different patients.
authors.affiliation: Department of Experimental Medicine and Immunotherapy, Institute for Applied Medical Engineering, University Hospital RWTH Aachen, Aachen, Germany.
authors.forename: Hannes
authors.initials: H
authors.lastname: Brehm
authors.affiliation: Department of Pharmaceutical Product Development, Fraunhofer Institute for Molecular Biology and Applied Ecology IME, Aachen, Germany.
authors.forename: Judith
authors.initials: J
authors.lastname: Niesen
authors.affiliation: Department of Experimental Medicine and Immunotherapy, Institute for Applied Medical Engineering, University Hospital RWTH Aachen, Aachen, Germany; Department of Pharmaceutical Product Development, Fraunhofer Institute for Molecular Biology and Applied Ecology IME, Aachen, Germany.
authors.forename: Radoslav
authors.initials: R
authors.lastname: Mladenov
authors.affiliation: Department of Experimental Medicine and Immunotherapy, Institute for Applied Medical Engineering, University Hospital RWTH Aachen, Aachen, Germany; Department of Pharmaceutical Product Development, Fraunhofer Institute for Molecular Biology and Applied Ecology IME, Aachen, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Stein
authors.affiliation: Department of Experimental Medicine and Immunotherapy, Institute for Applied Medical Engineering, University Hospital RWTH Aachen, Aachen, Germany.
authors.forename: Alessa
authors.initials: A
authors.lastname: Pardo
authors.affiliation: Department of Biology, Friedrich Alexander Universität Erlangen-Nürnberg, Germany.
authors.forename: Georg
authors.initials: G
authors.lastname: Fey
authors.affiliation: Laboratory for Translational Surgical Oncology, Department of Surgery, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands.
authors.forename: Wijnand
authors.initials: W
authors.lastname: Helfrich
authors.affiliation: Department of Pharmaceutical Product Development, Fraunhofer Institute for Molecular Biology and Applied Ecology IME, Aachen, Germany; Institute of Molecular Biotechnology (Biology VII), RWTH Aachen University, Aachen, Germany.
authors.forename: Rainer
authors.initials: R
authors.lastname: Fischer
authors.affiliation: Department of Pathology, Justus-Liebig University, Giessen, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Gattenlöhner
authors.affiliation: Department of Experimental Medicine and Immunotherapy, Institute for Applied Medical Engineering, University Hospital RWTH Aachen, Aachen, Germany; Department of Pharmaceutical Product Development, Fraunhofer Institute for Molecular Biology and Applied Ecology IME, Aachen, Germany. Electronic address: stefan.barth@ime.fraunhofer.de.
authors.forename: Stefan
authors.initials: S
authors.lastname: Barth
mesh_terms: D036002:ADP Ribose Transferases / Q000378:metabolism / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001427:Bacterial Toxins / Q000378:metabolism / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D011508:Chondroitin Sulfate Proteoglycans / Q000276:immunology* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005098:Exotoxins / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D000922:Immunotoxins / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D008565:Membrane Proteins / Q000276:immunology* / Q000378:metabolism; D011485:Protein Binding; D012208:Rhabdomyosarcoma / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D057127:Single-Chain Antibodies / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology*; D013997:Time Factors; D037521:Virulence Factors / Q000378:metabolism / Q000494:pharmacology*; D000097668:Pseudomonas aeruginosa Exotoxin A; D000099216:Chondroitin Sulfate Proteoglycan 4
chemical_list: D036002:ADP Ribose Transferases; D001427:Bacterial Toxins; D011508:Chondroitin Sulfate Proteoglycans; D005098:Exotoxins; D000922:Immunotoxins; D008565:Membrane Proteins; D057127:Single-Chain Antibodies; D037521:Virulence Factors; D000097668:Pseudomonas aeruginosa Exotoxin A; C101390:CSPG4 protein, human; D000099216:Chondroitin Sulfate Proteoglycan 4
keywords: CSPG4; Immunotherapy; Immunotoxin; Rhabdomyosarcoma