Development of new therapy for canine mammary cancer with recombinant measles virus.
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.
Laboratory Animal Research Center, Institute of Medical Science, University of Tokyo , Japan.
Koichiro
K
Shoji
Laboratory Animal Research Center, Institute of Medical Science, University of Tokyo , Japan.
Misako
M
Yoneda
Laboratory Animal Research Center, Institute of Medical Science, University of Tokyo , Japan.
Tomoko
T
Fujiyuki
Laboratory Animal Research Center, Institute of Medical Science, University of Tokyo , Japan.
Yosuke
Y
Amagai
Laboratories of Comparative Animal Medicine, Division of Animal Life Science, Tokyo University of Agriculture and Technology , Japan.
Akane
A
Tanaka
Laboratories of Veterinary Molecular Pathology and Therapeutics, Division of Animal Life Science, Tokyo University of Agriculture and Technology , Japan.
Akira
A
Matsuda
Department of Pathology, School of Life and Environmental Science, Azabu University , Japan.
Kikumi
K
Ogihara
Department of Pathology, School of Life and Environmental Science, Azabu University , Japan.
Yuko
Y
Naya
Laboratory Animal Research Center, Institute of Medical Science, University of Tokyo , Japan.
Fusako
F
Ikeda
Laboratories of Veterinary Molecular Pathology and Therapeutics, Division of Animal Life Science, Tokyo University of Agriculture and Technology , Japan.
Hiroshi
H
Matsuda
Laboratory Animal Research Center, Institute of Medical Science, University of Tokyo , Japan.
Hiroki
H
Sato
Laboratory Animal Research Center, Institute of Medical Science, University of Tokyo , Japan.
Chieko
C
Kai