Molecular Therapy: Oncolytics (Jan 2016)

Development of new therapy for canine mammary cancer with recombinant measles virus

  • Koichiro Shoji,
  • Misako Yoneda,
  • Tomoko Fujiyuki,
  • Yosuke Amagai,
  • Akane Tanaka,
  • Akira Matsuda,
  • Kikumi Ogihara,
  • Yuko Naya,
  • Fusako Ikeda,
  • Hiroshi Matsuda,
  • Hiroki Sato,
  • Chieko Kai

DOI
https://doi.org/10.1038/mto.2015.22
Journal volume & issue
Vol. 3, no. C

Abstract

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Oncolytic virotherapy is a promising treatment strategy for cancer. We previously generated a recombinant measles virus (rMV-SLAMblind) that selectively uses a poliovirus receptor-related 4 (PVRL4/Nectin4) receptor, but not signaling lymphocyte activation molecule (SLAM). We demonstrated that the virus exerts therapeutic effects against human breast cancer cells. Here, we examined the applicability of rMV-SLAMblind to treating canine mammary cancers (CMCs). We found that the susceptibilities of host cells to rMV-SLAMblind were dependent on canine Nectin-4 expression. Nectin-4 was detected in four of nine CMC cell lines. The rMV-SLAMblind efficiently infected those four Nectin-4-positive cell lines and was cytotoxic for three of them (CF33, CHMm, and CTBm). In vivo experiment showed that the administration of rMV-SLAMblind greatly suppressed the progression of tumors in mice xenografted with a CMC cell line (CF33). Immunohistochemistry revealed that canine Nectin-4 was expressed in 45% of canine mammary tumors, and the tumor cells derived from one clinical specimen were efficiently infected with rMV-SLAMblind. These results suggest that rMV-SLAMblind infects CMC cells and displays antitumor activity in vitro, in xenografts, and ex vivo. Therefore, oncolytic virotherapy with rMV-SLAMblind can be a novel method for treating CMCs.