Scientists have developed an antibody that significantly suppresses malignant tumours in dogs, showing promise for safe and effective treatment of intractable cancers.
As seen in humans, dogs have malignant or uncontrollable cancers that cannot be treated by existing therapies such as surgery, radiotherapy and chemotherapy. Oral malignant melanoma (OMM), a highly invasive cancer in dogs, is one such example.
In humans, some malignant cancer cells express PD-L1 proteins that bind to their receptor PD-1 on T cells, resulting in the suppression of the T cell's immune function.
The PD-L1/PD-1 interaction is considered an "immune escape mechanism" that cancer cells have.
Researchers from Hokkaido University in Japan developed a chimeric anti-PD-L1 antibody that induces immune responses and therefore tumour regression in dogs with malignant cancers.
The team first revealed that PD-L1 is expressed in the cells of OMM and another type of cancer called undifferentiated sarcoma, confirming that those two cancers are likely targeted by the immunotherapy.
They then utilised a rat anti-PD-L1 antibody to develop a rat-dog chimeric antibody which should help avoid rejection by the immune system and allergic reactions when administered to dogs.
Researchers treated seven dogs with OMM and two dogs with undifferentiated sarcoma were treated with the chimeric antibody every two weeks.
One of the OMM dogs showed obvious tumour regression after ten weeks of administration while one dog with undifferentiated sarcoma showed a significant decrease in tumour burden after three weeks.
Researchers found that none of them showed adverse effects such as an allergic reaction. Their data suggested the treatment may have prolonged survival in dogs with OMM after pulmonary metastasis.
"Chimerization of the antibody is now proven as a simple and effective strategy to develop therapeutic antibodies in veterinary medicine. Although further clinical studies are needed, other PD-L1-positive cancers could be targeted by the antibody we have developed," said Satoru Konnai from Hokkaido University.
"Given the similarity between humans and dogs in cancer biology, our study should provide a beneficial model for human preclinical studies," Konnai added.
The study was published in the journal Scientific Reports.
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