title: Antibody-based fusion proteins to target death receptors in cancer.
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.
authors.affiliation: Department of Surgery, Surgical Research Laboratories, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands.
authors.forename: Marco
authors.initials: M
authors.lastname: de Bruyn
authors.forename: Edwin
authors.initials: E
authors.lastname: Bremer
authors.forename: Wijnand
authors.initials: W
authors.lastname: Helfrich
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology*; D017209:Apoptosis; D002462:Cell Membrane / Q000378:metabolism; D004195:Disease Models, Animal; D053222:Fas Ligand Protein / Q000378:metabolism; D005260:Female; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D008024:Ligands; D008297:Male; D009369:Neoplasms / Q000188:drug therapy / Q000276:immunology*; D053218:Receptors, Death Domain / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000494:pharmacology*; D015398:Signal Transduction
chemical_list: D000906:Antibodies; D053222:Fas Ligand Protein; D008024:Ligands; D053218:Receptors, Death Domain; D011993:Recombinant Fusion Proteins