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Biochem Biophys Res Commun. 2004 Sep 10;322(1):197-202.

Increased cytotoxicity of soluble Fas ligand by fusing isoleucine zipper motif.

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Department of Neurosurgery, Faculty of Medicine, Saga University, Japan.


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.

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