Development of new therapy for canine mammary cancer with recombinant measles virus
Development of new therapy for canine mammary cancer with recombinant measles virus
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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 elbeco adu ripstop pants 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 sheepshead bay boats 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.