RRC ID |
31881
|
著者 |
Tone Y, Kawahara M, Kawaguchi D, Ueda H, Nagamune T.
|
タイトル |
Death signalobody: inducing conditional cell death in response to a specific antigen.
|
ジャーナル |
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.
|
巻・号 |
24(3)
|
ページ |
141-50
|
公開日 |
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
|
引用数 |
7
|
WOS 分野
|
MEDICINE, RESEARCH & EXPERIMENTAL
BIOTECHNOLOGY & APPLIED MICROBIOLOGY
GENETICS & HEREDITY
|
リソース情報 |
遺伝子材料 |
pRx hFAS-i-hCD25 (RDB01702) |