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Targeting the fetal acetylcholine receptor in rhabdomyosarcoma

: Simon-Keller, K.; Barth, S.; Vincent, A.; Marx, A.


Expert opinion on therapeutic targets 17 (2013), Nr.2, S.127-138
ISSN: 1472-8222
ISSN: 1744-7631
Fraunhofer IME ()

Introduction: Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma of childhood and adolescence. Recent efforts to enhance overall survival of patients with clinically advanced RMS have failed and there is a demand for conceptually novel treatments. Immune therapeutic options targeting the fetal nicotinic acetylcholine receptor (fnAChR), which is broadly expressed on RMS, are novel approaches to overcome the therapeutic resistance of RMS. Expression of the fnAChR is restricted to developing fetal muscles, some apparently dispensable ocular muscle fibers and thymic myoid cells. Therefore, after-birth fnAChR is a tumor-associated and almost tumor-specific antigen on RMS cells.
Areas covered: This review gives an overview on nAChR function and expression pattern in RMS tumor cells, and deals with the immunological significance of fnAChR-expressing cells, including the risk of anti-nAChR autoimmunity as a potential side effect of fnAChR-directed immunotherapies. Th e article also addresses the advantages and disadvantages of vaccination strategies, immunotoxins and chimeric T cells targeting the fnAChR.
Expert opinion: Finally, we suggest technical and biological strategies to improve the available immunotherapeutic tools including increasing the in vivo expression of the target fnAChR on RMS cells.