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Rhabdomyosarcoma Lysis by T Cells Expressing a Human Autoantibody-Based Chimeric Receptor Targeting the Fetal Acetylcholine Receptor

¹ Institute of Pathology, University of Wuerzburg, Wuerzburg, Germany; ² Department of Pediatric Hematology and Oncology, University Children's Hospital Münster, Münster, Germany; and ³ Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom

Requests for reprints: Stefan Gattenlöhner, Institute of Pathology, University of Wuerzburg, Josef-Schneider-Str. 2, D-97080 Wuerzburg, Germany. Phone: 49-931-201-47793; Fax: 49-931-201-47440; E-mail: stefan.gattenloehner{at}mail.uni-wuerzburg.de.

Rhabdomyosarcomas are the most frequent malignant soft tissue tumors of childhood; however, because current multimodality treatments fail to improve the poor survival rate of children with metastatic rhabdomyosarcoma, new treatments are required. We previously identified the -subunit of the fetal acetylcholine receptor (fAChR) as a specific cell surface target in rhabdomyosarcoma. Here, we engineered human T lymphocytes to express chimeric receptors composed of the antigen-binding domain of a human anti-fAChR antibody joined to the signaling domain of the human T-cell receptor -chain. The interaction of fAChR-transduced T cells with fAChR-positive rhabdomyosarcoma cell lines, but not with fAChR-negative control cells, induced T-cell activation characterized by strong secretion of IFN- and delayed lysis of tumor cells. Importantly, we found that in six of six rhabdomyosarcoma patients, chemotherapy increased fAChR expression on residual tumor cells in vivo. Our observations suggest that these fully human chimeric fAChR-transduced T cells, which should be well tolerated by the patient, have potential use in vivo both as a primary treatment for rhabdomyosarcoma and as a complementary approach to eradicate residual tumor cells after chemotherapy. (Cancer Res 2006; 66(1): 24-28)

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