| Literature DB >> 15313191 |
Tetsuya Shiraishi1, Kenji Suzuyama, Hiroaki Okamoto, Toshihiro Mineta, Kazuo Tabuchi, Kazuyuki Nakayama, Yusuke Shimizu, Junko Tohma, Takuo Ogihara, Hiroyasu Naba, Hidenori Mochizuki, Shigekazu Nagata.
Abstract
Fas (CD95) ligand (FasL) has the ability to induce apoptosis in Fas-expressing glioma cells by binding to Fas. Several molecular species have been designed to be soluble Fas ligands for therapeutic purposes. We successfully constructed a chimeric soluble FasL by fusing an isoleucine zipper motif for self-oligomerization and a FLAG sequence to the extracellular domain of the human Fas ligand (FIZ-shFasL). The cytotoxic effect of FIZ-shFasL on Jurkat cells was equivalent to that of membrane-bound FasL and approximately 10-fold stronger than that of agonistic anti-Fas antibody (CH-11). Flow cytometric analysis demonstrated that the differential Fas expression of human brain tumor cell lines partially correlated with levels of apoptosis through FIZ-shFasL. The upper limit of FIZ-shFasL for safe systemic administration to rat is estimated as below 2 microg/ml in plasma concentration. FIZ-shFasL could be applicable as a therapeutic agent for cancer.Entities:
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Year: 2004 PMID： 15313191 DOI： 10.1016/j.bbrc.2004.07.098
Source DB: PubMed Journal: Biochem Biophys Res Commun ISSN： 0006-291X Impact factor: 3.575