IMR Press / FBL / Volume 13 / Issue 6 / DOI: 10.2741/2847

Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.

Open Access Article
New cancer therapy using genetically-engineered oncolytic Sendai virus vector
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1 DNAVEC Corporation, 1-25-11 Kannondai, Tsukuba-shi, Ibaraki 305-0856, Japan
2 Department of Gene Therapy at the 21st Century COE program, Chiba University Graduate School of Medicine, Japan

Academic Editor: Masatoshi Tagawa

Front. Biosci. (Landmark Ed) 2008, 13(6), 2327–2334; https://doi.org/10.2741/2847
Published: 1 January 2008
(This article belongs to the Special Issue Current gene therapy for cancer)
Abstract

We have developed a new type of Sendai virus-(SeV) based gene transfer vectors for cancer therapy. The matrix gene-, indispensable for particle formation, deficient and fusion gene-, essential for cell-fusion and deciding viral tropism, redesigned SeV vector loses vector particle formation from transduced cells and gains cell-to-cell spreading in protease-dependent, namely controllable, manner. For the selective delivery to malignant tumor cells expressing matrix metalloproteinases (MMPs) or urokinase-type plasminogen activator (uPA), we introduced MMP-cleavage (PLGMTS) or uPA-cleavage (SGRS) sequences, respectively, immediately prior to the cleavage site for activation of fusion protein with remaining essential sequences for cell-fusion. The MMP-targeted SeV vector demonstrated syncytia formation in MMP expressing HT1080 cell line in vitro, and growth inhibition of HT1080 subcutaneous xenografts in vivo. The uPA-targeted one showed the same effects in uPA expressing PC-3 cell line. Severe apoptosis occurred in fused-cells. Thus, the vector selectively spreads to tumor cells in tumor-protease dependent manner and demonstrates the antitumor effects in solid tumors, indicating the value of selective targeting and killing of tumors by recombinant SeV technology.

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