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Updated: Mar 22, 2026
Paramyxoviruses for Tumor-targeted Immunomodulation: Design and Evaluation Ex Vivo
Published on: January 7, 2019
Development of new therapy for canine mammary cancer with recombinant measles virus
Koichiro Shoji1, Misako Yoneda1, Tomoko Fujiyuki1
1Laboratory Animal Research Center, Institute of Medical Science, University of Tokyo , Japan.
Abstract:
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.
Insights
Recombinant measles virus (rMV-SLAMblind) shows promise for treating canine mammary cancers. This virus selectively targets Nectin-4 receptors on cancer cells, demonstrating significant antitumor activity in preclinical models.
Area of Science:
- Oncolytic virotherapy
- Veterinary oncology
- Virology
Background:
- Oncolytic virotherapy offers a novel cancer treatment approach.
- A recombinant measles virus (rMV-SLAMblind) was engineered to target the poliovirus receptor-related 4 (PVRL4/Nectin4) receptor, avoiding signaling lymphocyte activation molecule (SLAM) receptors.
- Previous studies confirmed its efficacy against human breast cancer cells.
Purpose of the Study:
- To evaluate the potential of rMV-SLAMblind for treating canine mammary cancers (CMCs).
- To assess the susceptibility of CMC cells to rMV-SLAMblind based on Nectin-4 expression.
- To determine the in vitro and in vivo antitumor activity of rMV-SLAMblind against CMCs.
Main Methods:
- Assessed canine Nectin-4 expression in CMC cell lines and clinical samples.
- Infected Nectin-4-positive CMC cell lines with rMV-SLAMblind to evaluate infectivity and cytotoxicity.
- Administered rMV-SLAMblind to mice bearing CMC xenografts to assess in vivo efficacy.
- Utilized immunohistochemistry to confirm Nectin-4 expression in canine mammary tumors.
Main Results:
- Canine Nectin-4 expression varied among CMC cell lines, with four of nine being positive.
- rMV-SLAMblind efficiently infected Nectin-4-positive CMC cell lines and exhibited cytotoxicity in three (CF33, CHMm, CTBm).
- In vivo studies showed significant suppression of CMC xenograft tumor progression by rMV-SLAMblind.
- Canine Nectin-4 was expressed in 45% of canine mammary tumors, and tumor cells from a clinical specimen were infected by the virus.
Conclusions:
- rMV-SLAMblind demonstrates infectivity and antitumor activity against canine mammary cancer cells in vitro, in xenografts, and ex vivo.
- The virus's efficacy is linked to canine Nectin-4 expression levels.
- Oncolytic virotherapy using rMV-SLAMblind presents a potential new treatment strategy for canine mammary cancers.
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