A CSPG4-specific immunotoxin kills rhabdomyosarcoma cells and binds to primary tumor tissues

Hannes Brehm; Judith Niesen; Radoslav Mladenov; Christoph Stein; Alessa Pardo; Georg Fey; Wijnand Helfrich; Rainer Fischer; Stefan Gattenlöhner; Stefan Barth

doi:10.1016/j.canlet.2014.07.006

A CSPG4-specific immunotoxin kills rhabdomyosarcoma cells and binds to primary tumor tissues

Cancer Lett. 2014 Oct 1;352(2):228-35. doi: 10.1016/j.canlet.2014.07.006. Epub 2014 Jul 10.

Authors

Affiliations

¹ Department of Experimental Medicine and Immunotherapy, Institute for Applied Medical Engineering, University Hospital RWTH Aachen, Aachen, Germany.
² Department of Pharmaceutical Product Development, Fraunhofer Institute for Molecular Biology and Applied Ecology IME, Aachen, Germany.
³ 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.
⁴ Department of Biology, Friedrich Alexander Universität Erlangen-Nürnberg, Germany.
⁵ Laboratory for Translational Surgical Oncology, Department of Surgery, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands.
⁶ 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.
⁷ Department of Pathology, Justus-Liebig University, Giessen, Germany.
⁸ 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.

PMID: 25016058
DOI: 10.1016/j.canlet.2014.07.006

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.

Keywords: CSPG4; Immunotherapy; Immunotoxin; Rhabdomyosarcoma.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

ADP Ribose Transferases / metabolism
ADP Ribose Transferases / pharmacology*
Apoptosis / drug effects*
Bacterial Toxins / metabolism
Bacterial Toxins / pharmacology*
Cell Line, Tumor
Cell Survival / drug effects
Chondroitin Sulfate Proteoglycans / immunology*
Chondroitin Sulfate Proteoglycans / metabolism
Dose-Response Relationship, Drug
Exotoxins / metabolism
Exotoxins / pharmacology*
Humans
Immunotoxins / immunology
Immunotoxins / metabolism
Immunotoxins / pharmacology*
Inhibitory Concentration 50
Membrane Proteins / immunology*
Membrane Proteins / metabolism
Protein Binding
Pseudomonas aeruginosa Exotoxin A
Rhabdomyosarcoma / immunology
Rhabdomyosarcoma / metabolism
Rhabdomyosarcoma / pathology*
Single-Chain Antibodies / immunology
Single-Chain Antibodies / metabolism
Single-Chain Antibodies / pharmacology*
Time Factors
Virulence Factors / metabolism
Virulence Factors / pharmacology*

Substances

Bacterial Toxins
CSPG4 protein, human
Chondroitin Sulfate Proteoglycans
Exotoxins
Immunotoxins
Membrane Proteins
Single-Chain Antibodies
Virulence Factors
ADP Ribose Transferases