Grants - Pennsylvania - Designated Grants - 2018

Nicola Mason, DVM, Ph.D. & Dana Clarke, VMD, DACECC

Funded in partnership with the American Kennel Club Canine Health Foundation

Bladder cancer or urothelial carcinoma (UC) affects approximately 40,000 dogs per year in the US with specific breeds including Scottish Terriers, West Highland White Terriers, Shetland Sheepdogs, Beagles, and Parson Russell Terriers being over-represented. Affected dogs usually display lower urinary tract clinical signs including bloody urine, frequent urination, difficulty and pain on urinating, and urinary outflow tract obstruction. Standard of care consists of anti-inflammatory drugs either alone or in combination with chemotherapy or radiation therapy. While these treatments can lead to stable disease for 6-12 months, they rarely lead to a cure, and most dogs eventually succumb to their disease. In human medicine, urinary bladder tumors have been shown to exhibit a high gene mutational burden which directly correlates with a favorable response to immune therapies. Canine UC exhibits a similar mutational load suggesting that the disease in dogs may also be immune responsive. In this study, the investigators will evaluate the safety and effectiveness of a novel targeted, immune therapy that aims to promote a powerful immune response against a specific gene mutation (V600E B-Raf) recently identified in up to 87% of dogs with UC. The investigators hypothesize that vaccine-induced anti-tumor immune responses will lead to tumor regression and that such favorable responses will correlate with the baseline mutational burden of the tumor. The investigators will use standard immunological methods and advanced genetic sequencing technology to study systemic and intra-tumoral immune responses to identify biomarkers that may predict immunological and clinical response in dogs.