1. Targeted killing of rhabdomyosarcoma cells by a MAP-based human cytolytic fusion protein
- Author
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Hannes Brehm, Rainer Fischer, Stefan Barth, Dmitrij Hristodorov, Judith Niesen, Alessa Pardo, Radoslav Mladenov, and Mehmet Kemal Tur
- Subjects
Cancer Research ,Recombinant Fusion Proteins ,medicine.medical_treatment ,Apoptosis ,Biology ,Cholinergic Antagonists ,In vivo ,Cell Line, Tumor ,Rhabdomyosarcoma ,Escherichia coli ,medicine ,Humans ,Receptors, Cholinergic ,Receptor ,Cytotoxicity ,U937 Cells ,Immunotherapy ,medicine.disease ,Fusion protein ,In vitro ,Oncology ,Cancer research ,Camptothecin ,Microtubule-Associated Proteins ,Protein Binding - Abstract
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.
- Published
- 2015
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