March 15, 2017

WVC 2017: An Immunotherapy Vaccine for Canine Cancer

Dr. John Yannelli presented newer views on cancer treatment at the 2017 Western Veterinary Conference in Las Vegas, Nevada.
By Beth Thompson, VMD


An immunologist with more than 30 years of human cancer research experience, John Yanelli, PhD, discussed newer views on cancer treatment at the 2017 Western Veterinary Conference in Las Vegas, Nevada. Dr. Yannelli and his collaborator, Don Cohen, PhD, have shifted their focus at the University of Kentucky from human cancers to canine solid tumors.
 
As Dr. Yannelli reminded the conference audience, the immune system can and does distinguish cancerous cells from healthy cells. “Our bodies kill neoplastic cells every day,” he said, “long before any tumor develops.” Sometimes, even overt tumors that appear to have escaped the immune system disappear. In fact, Dr. Yannelli said, “about 2% of human melanomas spontaneously regress.” For some reason, the humoral and cell-mediated immunity that was initially “fooled” enough to suppress the tumor re-engages and successfully mounts a new attack on the mass. The more targeted and active the immune system is, the better the protection will be. Most often seen in patients with compromised, immature, or insufficient immune systems, neoplasia primarily affects the old, the immunosuppressed, and the young.
 
The Immune System Approach to Cancer
Immunotherapy that engages and activates natural immunity is an attractive approach to treatment because of its high specificity and minimal impact on normal tissues.  Vaccines use host immune machinery to generate anti-tumor effects, known as immunotherapy. Proof of that principle is well established in lung cancer clinical trials.
 
Detectable solid neoplasia has evaded the immune response. Much research concentrates on examining the multitude of methods tumors use to invoke and sustain evasion.
 
Evasion can and does happen even in the face of a competent immune system. Tumors may target antigen presentation, downregulate T-cell function, or produce immune suppressive substances, to name a few tactics. Tumors that are "under attack" by the immune system may mutate and make remaining cells less vulnerable to culling.
 
From Old Approaches to New Thinking
“Historically, we’ve approached cancer seeking a complete cure or, in other words, a disease-free state,” said Dr. Yannelli. Through the 1990s, a strong success rate utilizing aggressive treatments caused tumors to regress, but cancer was cured completely in only a small number of cases. The traditional approach—surgical debulking or removal of the mass followed by radiation and chemotherapy—was aimed at killing rapidly dividing cells. The unwanted side effects of that approach are collateral damage to healthy cells and compromise of overall patient health, quality of life, and well-being. What's more, these treatments are very time-consuming.
 
With the advent of successful medical management of formerly fatal diseases like HIV, the thinking has changed. Perhaps we should consider cancer as more of a chronic condition and induce an equilibrium state with the immune system in which tumors, although present, do not grow any larger and progressive illness remains delayed.
 
Before Dr. Yannelli and his laboratory started its work on dogs, their focus was late stage non–small cell lung cancer. In his immunotherapy work with 56 stage 3 or stage 4 patients followed over 6 or 7 years, 67% generated a response with immunotherapy. In 2005, he was part of the team that treated 21 patients with non–small cell cancer whose expected survival was 3 to 12 months. Thirteen of the original 21 patients returned for follow-up in 2011. The notable finding was that they survived all that time without any sign of tumor regression. Rather, the tumor existed in equilibrium with the person’s immune system.
 
Why Dogs?
Dr. Yannelli told the audience that he turned to dogs as research subjects in 2015. It made sense to him because dogs have an 80% genetic similarity to humans, while the more commonly used mice only have a 67% genetic similarity. Furthermore, if the immunotherapeutic intervention in people who had been told they had only months to live allowed them to survive for years, those same results in survival and quality of life would be much more significant in the shorter lifespan of our canine companions.
 
According to Dr. Yannelli, 6 million of 70 million dogs in the United States get cancer, including more than 50% of dogs over 10 years of age. Of those dogs stricken with cancer, 25% will die of the disease. Research with owners of these dogs shows that 20% of them seek advice, and 60% to 80% want to do something to help their pet. All the conventional cancer therapies available to humans are also available to dogs, but cost, quality of life, and the time required for therapy dissuade many owners from pursuing treatment.
 
Immunotherapy in the Fight Against Canine Cancer
Oncept, the only cancer vaccine licensed by the U.S. Department of Agriculture for use in dogs, works against oral melanoma. Dr. Yannelli and colleagues have used those and other learnings to develop a solid tumor vaccine for dogs (K9-ACV) suffering from any peripheral solid tumor that is accessible for surgical resection. Examples include hemangiosarcoma, mammary tumor, melanoma, squamous cell carcinoma, basal cell carcinoma, sebaceous gland tumor, rod cell tumor, and mast cell tumor.
 
The principle behind the intradermal vaccine is that it presents a “danger signal” to the patient’s antigen-presenting cells. That signal is designed specifically to make the patient’s tumor appear foreign and thereby induce both humoral and cellular immunity.
 
In the initial pilot study of 124 dogs, 54 were vaccinated and evaluated. Of those, 86% showed a measurable antibody response and 40% are alive and well today. Further clinical trials are currently under way at Kansas State University School of Veterinary Medicine, and the vaccine is available commercially for veterinary use.
 
More information about patient selection, sample submission, and cost of this autologous solid tumor vaccine is available at medivetbiologics.com.

 
Dr. Thompson is a small animal veterinarian, animal health executive, editor, and writer. She has held numerous positions with oversight responsibilities for editorial and business direction, including for Veterinary Learning Systems (publisher of Veterinary Technician and Compendium), Vetstreet.com, HealthyPet, and NAVC. 
 
 
 
 
 

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