Dogs act as an excellent translational model because they develop spontaneous cancers that behave similarly to their human counterparts clinically, and their response to treatment is comparable. They have the same cancer incidence as people, and it is the number one cause of death in dogs.
Many of the human oncology standard-of-care surgical, radiation, and chemotherapeutic protocols have been pioneered in canines, but there are only 3 registered immunotherapeutics for dogs in Australia, while immunotherapy is included as standard in the treatment of many human cancers.
Rodent pre-clinical translational models utilise genetically modified and immunodeficient animals, with low rate of success in new drug discovery. Natural dog models allow veterinary and human medical treatments to be developed in parallel, as canine tumours show real-life tumour evolution and spread under immune system surveillance and editing, but more information is needed regarding canine TME. TILs are an important prognosticator in the human cancers, but overlooked by veterinary pathologists as no standardised guidelines exist. This study sought to investigate the cytokines and leukocytes present in various canine tumours and any changes in these in response to treatment with a novel immunotherapeutic. Comparative results for safety, efficacy, candidate prioritisation, and proof of concept from this trial may lead to important translational findings for human cancer.
An excellent safety profile was established with over 170 intramuscular injections. Efficacy results demonstrated proof of concept with complete remission, complete remission with extended disease-free interval, extended overall survival, and stable disease recorded. FNA was validated as a collection method in comparison to more invasive surgical biopsies for cytokine gene expression profiling.
Cytokine expression was found to correlate with clinical responses, with responders treated with the comparator Rhizavidin showing a unique pattern. Potential biomarkers for response were identified, guiding further study into mechanisms of canine tumour immune evasion.