title: A measles virus selectively blind to signaling lymphocytic activation molecule shows anti-tumor activity against lung cancer cells.
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.
authors: Laboratory Animal Research Center, The Institute of Medical Science, The University of Tokyo, Shirokanedai, Minato-ku, Tokyo, 108-8639, Japan.
authors: Tomoko
authors: T
authors: Fujiyuki
authors: Laboratory Animal Research Center, The Institute of Medical Science, The University of Tokyo, Shirokanedai, Minato-ku, Tokyo, 108-8639, Japan.
authors: Misako
authors: M
authors: Yoneda
authors: Laboratory Animal Research Center, The Institute of Medical Science, The University of Tokyo, Shirokanedai, Minato-ku, Tokyo, 108-8639, Japan.
authors: Yosuke
authors: Y
authors: Amagai
authors: Laboratory Animal Research Center, The Institute of Medical Science, The University of Tokyo, Shirokanedai, Minato-ku, Tokyo, 108-8639, Japan.
authors: Kunie
authors: K
authors: Obayashi
authors: Laboratory Animal Research Center, The Institute of Medical Science, The University of Tokyo, Shirokanedai, Minato-ku, Tokyo, 108-8639, Japan.
authors: Fusako
authors: F
authors: Ikeda
authors: Laboratory Animal Research Center, The Institute of Medical Science, The University of Tokyo, Shirokanedai, Minato-ku, Tokyo, 108-8639, Japan.
authors: Koichiro
authors: K
authors: Shoji
authors: Division of Molecular Pathology, The Institute of Medical Science, The University of Tokyo, Shirokanedai, Minato-ku, Tokyo, 108-8639, Japan.
authors: Yoshinori
authors: Y
authors: Murakami
authors: Laboratory Animal Research Center, The Institute of Medical Science, The University of Tokyo, Shirokanedai, Minato-ku, Tokyo, 108-8639, Japan.
authors: Hiroki
authors: H
authors: Sato
authors: Laboratory Animal Research Center, The Institute of Medical Science, The University of Tokyo, Shirokanedai, Minato-ku, Tokyo, 108-8639, Japan.
authors: Chieko
authors: C
authors: Kai
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000628:therapy* / Q000821:virology; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D005260:Female; D005434:Flow Cytometry; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000628:therapy* / Q000821:virology; D008459:Measles virus / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D016513:Mice, SCID; D008856:Microscopy, Fluorescence; D050130:Oncolytic Virotherapy / Q000379:methods*; D050504:Oncolytic Viruses / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1; D023041:Xenograft Model Antitumor Assays; D000075983:Nectins
chemical_list: D015703:Antigens, CD; D015815:Cell Adhesion Molecules; D049452:Green Fluorescent Proteins; D011956:Receptors, Cell Surface; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1; C442228:NECTIN4 protein, human; D000075983:Nectins
keywords: lung cancer; measles virus; nectin-4; oncolytic virus; virotherapy