DEVELOPMENT OF NEW THERAPY FOR CANINE MAMMARY CANCER WITH RECOMBINANT MEASLES VIRUS

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.

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