Oncotarget

Research Papers:

A measles virus selectively blind to signaling lymphocytic activation molecule shows anti-tumor activity against lung cancer cells

Tomoko Fujiyuki, Misako Yoneda, Yosuke Amagai, Kunie Obayashi, Fusako Ikeda, Koichiro Shoji, Yoshinori Murakami, Hiroki Sato and Chieko Kai _

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Oncotarget. 2015; 6:24895-24903. https://doi.org/10.18632/oncotarget.4366

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Abstract

Tomoko Fujiyuki1, Misako Yoneda1, Yosuke Amagai1, Kunie Obayashi1, Fusako Ikeda1, Koichiro Shoji1, Yoshinori Murakami2, Hiroki Sato1, Chieko Kai1

1Laboratory Animal Research Center, The Institute of Medical Science, The University of Tokyo, Shirokanedai, Minato-ku, Tokyo, 108-8639, Japan

2Division of Molecular Pathology, The Institute of Medical Science, The University of Tokyo, Shirokanedai, Minato-ku, Tokyo, 108-8639, Japan

Correspondence to:

Chieko Kai, e-mail: [email protected]

Keywords: measles virus, virotherapy, lung cancer, oncolytic virus, nectin-4

Received: January 04, 2015     Accepted: June 19, 2015     Published: June 30, 2015

ABSTRACT

Lung cancer cells, particularly those of non-small-cell lung cancer, are known to express Nectin-4. We previously generated a recombinant measles virus that uses Nectin-4 as its receptor but cannot bind its original principal receptor, signaling lymphocyte activation molecule (SLAM). This virus (rMV-SLAMblind) infects and kills breast cancer cells in vitro and in a subcutaneous xenograft model. However, it has yet to be determined whether rMV-SLAMblind is effective against other cancer types and in other tumor models that more closely represent disease. In this study, we analyzed the anti-tumor activity of this virus towards lung cancer cells using a modified variant that encodes green fluorescent protein (rMV-EGFP-SLAMblind). We found that rMV-EGFP-SLAMblind efficiently infected nine, human, lung cancer cell lines, and its infection resulted in reduced cell viability of six cell lines. Administration of the virus into subcutaneous tumors of xenotransplanted mice suppressed tumor growth. In addition, rMV-EGFP-SLAMblind could target scattered tumor masses grown in the lungs of xenotransplanted mice. These results suggest that rMV-SLAMblind is oncolytic for lung cancer and that it represents a promising tool for the treatment of this disease.


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