Antibody-based fusion proteins to target death receptors in cancer |
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Authors: | Marco de Bruyn Edwin BremerWijnand Helfrich |
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Institution: | Department of Surgery, Surgical Research Laboratories, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands |
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Abstract: | Ideally, an immunotoxin should be inactive ‘en route’, acquire activity only after tumor cell surface binding and have no off-target effects towards normal cells. In this respect, antibody-based fusion proteins that exploit the tumor-selective pro-apoptotic death ligands sFasL and sTRAIL appear promising. Soluble FasL largely lacks receptor-activating potential, whereas sTRAIL is inactive towards normal cells. Fusion proteins in which an anti-tumor antibody fragment (scFv) is fused to sFasL or sTRAIL prove to be essentially inactive when soluble, while gaining potent anti-tumor activity after selective binding to a predefined tumor-associated cell surface antigen. Importantly, off-target binding by scFv:sTRAIL to normal cells showed no signs of toxicity. In this review, we highlight the rationale and perspectives of scFv:TRAIL/scFv:sFasL based fusion proteins for cancer therapy. |
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Keywords: | TRAIL FasL scFv Immune therapy Targeting Apoptosis |
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