RRC ID 31881
Author Tone Y, Kawahara M, Kawaguchi D, Ueda H, Nagamune T.
Title Death signalobody: inducing conditional cell death in response to a specific antigen.
Journal Hum Gene Ther Methods
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.
Volume 24(3)
Pages 141-50
Published 2013-6-1
DOI 10.1089/hgtb.2012.147
PMID 23470213
MeSH Animals Antigen-Antibody Complex Antigens / immunology Antigens / metabolism Apoptosis* Cell Line Cell Survival Fluorescein / chemistry Fluorescein / metabolism Genetic Vectors / genetics Genetic Vectors / metabolism Humans Mice Recombinant Fusion Proteins / genetics* Recombinant Fusion Proteins / metabolism Retroviridae / genetics Serum Albumin, Bovine / chemistry Serum Albumin, Bovine / metabolism Single-Chain Antibodies / genetics* Single-Chain Antibodies / metabolism Transduction, Genetic fas Receptor / genetics* fas Receptor / metabolism
IF 2.446
Times Cited 7
DNA material pRx hFAS-i-hCD25 (RDB01702)