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Journal of Biomedicine and Biotechnology
Volume 2010, Article ID 187621, 11 pages
http://dx.doi.org/10.1155/2010/187621
Research Article

A Human Recombinant Autoantibody-Based Immunotoxin Specific for the Fetal Acetylcholine Receptor Inhibits Rhabdomyosarcoma Growth In Vitro and in a Murine Transplantation Model

1Institute of Pathology, University of Würzburg, 97080 Würzburg, Germany
2Department of Pharmaceutical Product Development, Fraunhofer Institute for Molecular Biology and Applied Ecology, Forckenbeckstraße 6, 52074 Aachen, Germany
3Neurosciences Group, Department of Clinical Neurology, Weatherall Institute of Molecular Medicine, University of Oxford, OX3 9DU Oxford, UK
4Hellenic Pasteur Institute, 127, Vas. Sofias Avenue 11521, Athens, Greece
5Department of Pediatric Oncology, Olga Hospital, 70176 Stuttgart, Germany
6Department of Experimental Medicine and Immunotherapy, Helmholtz-Institute for Biomedical Engineering, University Hospital RWTH Aachen, Pauwelsstraße 20, 52074 Aachen, Germany
7Institute of Pathology, University Medical Center Mannheim, University of Heidelberg, Theodor-Kutzer Ufer 1-3, 68135 Mannheim, Greece

Received 14 August 2009; Accepted 18 November 2009

Academic Editor: Rene Anand

Copyright © 2010 S. Gattenlöhner et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Rhabdomyosarcoma (RMS) is the most common malignant soft tissue tumor in children and is highly resistant to all forms of treatment currently available once metastasis or relapse has commenced. As it has recently been determined that the acetylcholine receptor (AChR) -subunit, which defines the fetal AChR (fAChR) isoform, is almost exclusively expressed in RMS post partum, we recombinantly fused a single chain variable fragment (scFv) derived from a fully human anti-fAChR Fab-fragment to Pseudomonas exotoxin A to generate an anti-fAChR immunotoxin (scFv35-ETA). While scFv35-ETA had no damaging effect on fAChR-negative control cell lines, it killed human embryonic and alveolar RMS cell lines in vitro and delayed RMS development in a murine transplantation model. These results indicate that scFv35-ETA may be a valuable new therapeutic tool as well as a relevant step towards the development of a fully human immunotoxin directed against RMS. Moreover, as approximately 20% of metastatic malignant melanomas (MMs) display rhabdoid features including the expression of fAChR, the immunotoxin we developed may also prove to be of significant use in the treatment of these more common and most often fatal neoplasms.