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: Tomoko Fujiyuki, Misako Yoneda, Yosuke Amagai, Kunie Obayashi, Fusako Ikeda, Koichiro Shoji, Yoshinori Murakami, Hiroki Sato, Chieko Kai
• Journal: Oncotarget (Oncotarget) Vol. 6 Issue 28 Pg. 24895-903 (Sep 22 2015) ISSN: 1949-2553 [Electronic] United States
• PMID: 26317644 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, CD
• Cell Adhesion Molecules
• Receptors, Cell Surface
• NECTIN4 protein, human
• Green Fluorescent Proteins
• Signaling Lymphocytic Activation Molecule Family Member 1

Topics

• Animals
• Antigens, CD (genetics, metabolism)
• Carcinoma, Non-Small-Cell Lung (genetics, therapy, virology)
• Cell Adhesion Molecules (genetics, metabolism)
• Cell Line, Tumor
• Female
• Flow Cytometry
• Green Fluorescent Proteins (genetics, metabolism)
• Humans
• Lung Neoplasms (genetics, therapy, virology)
• Measles virus (genetics, metabolism, physiology)
• Mice, SCID
• Microscopy, Fluorescence
• Oncolytic Virotherapy (methods)
• Oncolytic Viruses (genetics, metabolism, physiology)
• Receptors, Cell Surface (genetics, metabolism)
• Signaling Lymphocytic Activation Molecule Family Member 1
• Xenograft Model Antitumor Assays