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Targeted killing of rhabdomyosarcoma cells by a MAP-based human cytolytic fusion protein

: Brehm, H.; Hristodorov, D.; Pardo, A.; Mladenov, R.; Niesen, J.; Fischer, R.; Tur, M.K.; Barth, S.


Cancer letters 365 (2015), No.2, pp.149-155
ISSN: 0304-3835
ISSN: 1872-7980
Journal Article
Fraunhofer IME ()

The treatment of rhabdomyosarcoma (RMS) is challenging, and the prognosis remains especially poor for high-grade RMS with metastasis. The conventional treatment of RMS is based on multi-agent chemotherapy combined with resection and radiotherapy, which are often marked by low success rate. Alternative therapeutic options include the combination of standard treatments with immunotherapy. We generated a microtubule-associated protein (MAP)-based fully human cytolytic fusion protein (hCFP) targeting the fetal acetylcholine receptor, which is expressed on RMS cells. We were able to express and purify functional scFv35-MAP from Escherichia coli cells. Moreover, we found that scFv35-MAP is rapidly internalized by target cells after binding its receptor, and exhibits specific cytotoxicity toward FL-OH1 and RD cells in vitro. We also confirmed that scFv35-MAP induces apoptosis in FL-OH1 and RD cells. The in vivo potential of scFv35-MAP will need to be considered in further studies.