New expected objective for treating metastasized oral malignant melanoma in dogs

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• Source: Hokkaido University


• Date: 23 Apr,2021

Scientists have shown that the biological molecule PD-L1 is a possible target for the treatment of metastasized oral malignant melanoma in dogs.

There are a number of cancers that affect dogs, but there are far fewer diagnosis and treatment options for these canine cancers. However, because dogs and humans are both mammals, it is very likely that strategies and treatments for cancers in humans may be used for canine cancer, with minor modifications.

A group of scientists, including Associate Professor Satoru Konnai in the Faculty of Veterinary Medicine at Hokkaido University, have shown that an anti-cancer therapy that targets the cancer marker PD-L1–a goal that has shown great promise for treating cancer in humans–is successful for canine cancer also. Their findings were published in the journal npj Precision Oncology.

The proteins Programmed Cell Death 1 (PD-1) and its associated molecule, PD-ligand 1 (PD-L1) are involved in the immune response in people. PD-L1 is overexpressed by many kinds of cancer in people, allowing these cancers to suppress the immune reaction.

Studies in mice models and in human cell lines have demonstrated that PD-1 and PD-L1 have great promise in the treatment of cancer as blocking them strengthens the immune response to cancer.

Malignant melanomas are a canine cancer that is both relatively common and fatal. In particular, oral malignant melanomas (OMMs) are highly invasive and metastatic; with treatment, the median survival time is less than two weeks. As new treatments are necessary for this cancer, the scientists decided to explore the options available.

The scientists first developed a book anti-PD-L1 monoclonal antibody to detect PD-L1 in various canine cancers by immunohistochemical staining. Using this antibody, they demonstrated that malignant canine cancers expressed PD-L1; out of 20 samples for each cancer tested, nasal adenocarcinoma, transitional cell carcinoma, osteosarcoma and mammary adenocarcinoma had a 100% positive rate, while rectal sac gland carcinoma and OMM had a 95% positive rate.

A former pilot study had shown that another canine chimeric anti-PD-L1 monoclonal antibody had anti-tumor influence against OMM, when tested on nine dogs.

For the current research scientists picked 29 dogs with primary OMM and pulmonary metastasis, where the melanoma has spread to the lungs, and most of that had been exposed to one round of treatment. These dogs were treated with the chimeric antibody every 2 weeks, along with other interventions to attain local control of cancer were allowed.

The survival time of dogs treated with the chimeric antibody was significantly longer, with a median survival period of 143 days, compared to 54 days for the control group, from historic data.

Five dogs showed tumor response, where the tumor decreased or disappeared due to the treatment. In one of them, all detectable tumors vanished. In two other dogs, all detectable tumors disappeared, leading to survival times more than a year.

The increase in survival time correlated positively with radiation therapy that was simultaneous or started within eight weeks of therapy with the chimeric antibody.

Our findings are limited by the small size of the historical control group. Nevertheless, as there is no systemic therapy that prolongs the survival of dogs with pulmonary metastatic OMM, the increased survival time encourages the further development of anti-PD-L1 therapy in dogs.”

Satoru Konnai, Associate Professor, Faculty of Veterinary Medicine, Hokkaido University