title: Death signalobody: inducing conditional cell death in response to a specific antigen.
abstract: As the possibility of tumorigenesis and undesirable immune responses in patients cannot be completely excluded in gene and cell therapies, a conditional death switch to eliminate the therapeutic cells would be a valuable tool to enhance the safety of these therapies. A few ligand-receptor conditional death switches have already been developed; however, they cannot be used if patients exhibit side effects upon administration of the ligand. Here we demonstrate a death-inducing chimeric antibody named "death signalobody," in which the antigen-antibody system, having virtually infinite ligand-receptor combinations, is utilized for the activation of death signaling. We designed a death signalobody named "SFas," which has an antifluorescein single-chain variable fragment and the cytoplasmic domain of Fas. SFas efficiently induced conditional apoptosis in murine pro-B Ba/F3 cells in response to fluorescein-conjugated bovine serum albumin. Moreover, SFas was also able to induce antigen-dependent conditional apoptosis in human cancer cell lines. The death signalobody technique will be a valuable tool for the conditional elimination of cells of interest in multiple therapeutic applications.
authors.affiliation: Department of Chemistry and Biotechnology, School of Engineering, The University of Tokyo, Tokyo 113-8656, Japan.
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Tone
authors.forename: Masahiro
authors.initials: M
authors.lastname: Kawahara
authors.forename: Daichi
authors.initials: D
authors.lastname: Kawaguchi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ueda
authors.forename: Teruyuki
authors.initials: T
authors.lastname: Nagamune
mesh_terms: D000818:Animals; D000936:Antigen-Antibody Complex; D000941:Antigens / Q000276:immunology / Q000378:metabolism; D017209:Apoptosis; D002460:Cell Line; D002470:Cell Survival; D019793:Fluorescein / Q000737:chemistry / Q000378:metabolism; D005822:Genetic Vectors / Q000235:genetics / Q000378:metabolism; D006801:Humans; D051379:Mice; D011993:Recombinant Fusion Proteins / Q000235:genetics* / Q000378:metabolism; D012190:Retroviridae / Q000235:genetics; D012710:Serum Albumin, Bovine / Q000737:chemistry / Q000378:metabolism; D057127:Single-Chain Antibodies / Q000235:genetics* / Q000378:metabolism; D014161:Transduction, Genetic; D019014:fas Receptor / Q000235:genetics* / Q000378:metabolism
chemical_list: D000936:Antigen-Antibody Complex; D000941:Antigens; C491901:FAS protein, human; D011993:Recombinant Fusion Proteins; D057127:Single-Chain Antibodies; D019014:fas Receptor; D012710:Serum Albumin, Bovine; D019793:Fluorescein