1. A CSPG4-specific immunotoxin kills rhabdomyosarcoma cells and binds to primary tumor tissues
- Author
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Wijnand Helfrich, Rainer Fischer, Judith Niesen, Stefan Barth, Hannes Brehm, Georg H. Fey, Radoslav Mladenov, Christoph Stein, Stefan Gattenlöhner, Alessa Pardo, Targeted Gynaecologic Oncology (TARGON), Translational Immunology Groningen (TRIGR), and Publica
- Subjects
Cancer Research ,Time Factors ,genetic structures ,medicine.medical_treatment ,Apoptosis ,chemistry.chemical_compound ,FACTOR-I RECEPTOR ,Immunotoxin ,Rhabdomyosarcoma ,MOLECULAR CHARACTERIZATION ,ADP Ribose Transferases ,Chemistry ,Immunotoxins ,ANTIBODY-BASED IMMUNOTHERAPY ,musculoskeletal system ,Primary tumor ,NUDE-MICE ,Oncology ,Alveolar rhabdomyosarcoma ,Immunotherapy ,Protein Binding ,musculoskeletal diseases ,EXPRESSION ,CSPG4 ,Cell Survival ,Virulence Factors ,Bacterial Toxins ,Exotoxins ,MELANOMA-ASSOCIATED ANTIGEN ,Inhibitory Concentration 50 ,Cell Line, Tumor ,medicine ,Humans ,BREAST-CANCER ,SINGLE-CHAIN IMMUNOTOXIN ,Chondroitin Sulfate Proteoglycan 4 ,CHONDROITIN SULFATE PROTEOGLYCAN ,Dose-Response Relationship, Drug ,Membrane Proteins ,medicine.disease ,eye diseases ,Chondroitin Sulfate Proteoglycans ,Chondroitin sulfate proteoglycan ,Cancer research ,ALVEOLAR RHABDOMYOSARCOMA ,human activities ,Single-Chain Antibodies - Abstract
The treatment of rhabdomyosarcoma (RMS) remains challenging, with metastatic and alveolar RMS offering a particularly poor prognosis. Therefore, the identification and evaluation of novel antigens, which are suitable targets for immunotherapy, is one attractive possibility to improve the treatment of this disease. Here we show that chondroitin sulfate proteoglycan 4 (CSPG4) is expressed on RMS cell lines and RMS patient material. We evaluated the immunotoxin (IT) αMCSP-ETA', which specifically recognizes CSPG4 on the RMS cell lines RD, FL-OH1, TE-671 and Rh30. It is internalized rapidly, induces apoptosis and thus kills RMS cells selectively. We also demonstrate the specific binding of this IT to RMS primary tumor material from three different patients.
- Published
- 2014