A research group led by Specially appointment assistant prof. Naoya Maekawa and Satoru Konnai (Hokkaido University) established an immunohistochemical staining method specifically detecting canine PD-L1 and demonstrated that treatment with anti-PD-L1 antibodies, an immune checkpoint inhibitor, showed certain efficacy and safety in dogs with lung-metastatic malignant melanoma.
In recent years, as dogs live longer, more are dying from malignant tumors (cancer). Beyond existing treatments, there is a growing need for new therapeutic strategies. In human medicine, alongside surgery, radiation therapy, and chemotherapy, immunotherapy applications are advancing. Specifically, immune checkpoint inhibitors like anti-PD-1 antibodies and anti-PD-L1 antibodies have shown favorable treatment outcomes for many cancer types, including malignant melanoma and lung cancer. We have previously demonstrated that immune suppression via the PD-1/PD-L1 pathway also occurs in canine malignant tumors. Furthermore, it has been shown that the canine chimeric anti-PD-L1 antibody (c4G12), the world’s first immune checkpoint inhibitor for dogs, induces tumor regression in some dogs. However, limited information exists regarding which tumors express PD-L1 and are suitable treatment targets, as well as the therapeutic efficacy and safety of anti-PD-L1 antibodies, necessitating larger-scale investigations.
Therefore, in this study, we first established an immunohistochemical staining method specifically detecting canine PD-L1 and performed expression analysis. This revealed high rates of PD-L1 expression in various types of cancer, including malignant melanoma. Furthermore, when experimental treatment with anti-PD-L1 antibodies was administered to 29 dogs with malignant melanoma that had metastasized to the lungs, tumor regression, including in the lung metastases, was observed in some dogs. Compared to our previously treated cases, the anti-PD-L1 antibody treatment group showed significantly longer survival times. These findings represent a major step toward offering immunotherapy as a treatment option for canine tumors and provide important insights for the practical application of immune checkpoint inhibitors in dogs.
Part of this research was conducted in collaboration with Tohoku University under the support of the Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology and the AMED Drug Discovery and Other Life Science Research Support Infrastructure Project (Drug Discovery Support Technology Infrastructure Platform Project).
The results were published in Scientific Reports on February 12, 2021.
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