Seeking Longer Lives for Canine Companions 

Cancer doesn't discriminate. It's a devastating disease that affects many species—including canine family members. One fairly common cancer in dogs is oral melanoma, which is the most common malignant tumor found in dogs’ mouths, forming in cells of the mucous membranes. It’s often treated with surgery followed by radiation to remove as much of the tumor as possible. But it’s an aggressive, invasive cancer that can be difficult to fully eradicate, and it's frequently resistant to chemotherapy.1,2. It has a tendency to return after surgery and spread to the dog’s lymph nodes and internal organs3, often proving fatal. So conventional therapies just haven’t been sufficient; most dogs diagnosed with oral melanoma survived less than six months even with treatment4.

Until a couple of years ago, that is. Today Merial offers a promising adjunct treatment option that actually leverages dogs’ own immune systems to fight oral melanoma—delivering significantly longer post-surgery survival times.1  It’s the result of a years-long, multi-party collaboration—started when a team of human cancer researchers joined forces with one determined veterinarian…

Translating Human Research to Dogs 

Advances in veterinary medicine often emerge from research in human health. So in the early 2000s Dr. Philip Bergman, a veterinary oncologist looking for new ways to treat canine melanoma, reached out to a team of researchers at Memorial Sloan Kettering Cancer Center working on a human vaccine for the same cancer. Conversations led to parallel vaccine trials in both humans and dogs—and before long, Dr. Bergman’s dog studies were proving effective enough to move to the next step. He approached Merial, knowing our commitment to pet care innovation, and we were intrigued by the team’s novel approach to using a vaccine as an adjunct therapy for cancer 

Training the Immune System to Fight Cancer

But there were challenges to face, around basic principles of biology. Vaccines are an immunotherapy, meaning they activate the body's own immune system to fight a disease, usually caused by outside agents such as viruses or bacteria. A vaccine contains an inactivated or partial version of the pathogen, or a substance associated with it—not enough to cause illness, but enough to trigger the immune system to create antibodies against the pathogen. While vaccines are most often used to prevent infection, some can be used to treat an already-existing state of disease.

Harnessing the immune system against cancer, however, is trickier, because cancer cells aren’t outside invaders like viruses and bacteria—they’re the body’s own cells. And because the body perceives cancer cells as "self," the immune system won’t attack them. The Memorial Sloan-Kettering team’s "ah-ha" moment came in the discovery that they could "trick" the dog's immune system. Noting that both human and canine melanoma cells have an enzyme called tyrosinase, the researchers used the human enzyme in the canine vaccine—thus triggering the dog's immune system against the foreign, human substance. Once in action, the dog's immune response continued to target ALL versions of tyrosinase—even canine—as well as the enzyme’s originating cancer cells. The key to this innovation was recognizing that human tyrosinase was different enough from canine to kickstart the dog's immune response, yet still similar enough to keep that response going against the canine cancer.

We’re very excited about continuing research into this vaccine to explore the potential implications it has for humans. We hope this will result in improved cancer treatment for all.

Jedd D. Wolchok, MD, PhD, Chief, Melanoma and Immunotherapeutics Service, Memorial Sloan Kettering Cancer Center

Partnering on Vaccine Delivery Technologies 

Once the science was established in controlled studies, the next hurdle was finding a reliable mode of vaccine delivery practical for wider commercial production and use. Here, Merial's industry connections played a key role. We turned first to Vical, a biotech company whose patented DNA technology offered an ideal solution, allowing us to insert a human gene encoded to produce the enzyme—rather than the enzyme itself—into a small circle of DNA. Once vaccinated, some of the dog’s cells take up that DNA and start producing the human enzyme themselves, triggering the critical immune response.

Finally, we wanted to simplify vaccine administration, so we partnered with medical device company Bioject, Inc. The resulting Canine Transdermal Device uses a high-powered spring to inject the vaccine smoothly into the dog's thigh muscle without a needle.

Bringing ONCEPT® Melanoma to Vets and Pets 

Our collaborations paid off: in 2007 the U.S. Department of Agriculture (USDA) granted a conditional Veterinary Biological Product License for the vaccine, which became known as ONCEPT Melanoma. This gave veterinary oncologists around the U.S. another weapon in their arsenal to start using against canine oral melanoma, along with surgery and radiation. In the meantime, with hopes of soon making ONCEPT Melanoma more widely available, we obtained full licensing rights from Memorial Sloan-Kettering and Dr. Bergman. And the Merial team continued close collaborations with Dr. Bergman to design and conduct field safety and efficacy trials in canine patients to test the new therapy further.

In 2010 the team completed its efficacy study report, which provided the evidence on ONCEPT Melanoma that the USDA required to grant full licensure to this first-of-its-kind therapeutic vaccine. Everyone involved was overjoyed that our years of hard work had come to fruition. Most importantly, thousands dogs across the U.S. with stage II or III oral melanoma were living longer once ONCEPT Melanoma was added as an adjunct therapy to their treatment regimen. And as the first-ever immunotherapeutic—in any species, animal or human—to actually contribute to treating a cancer, ONCEPT Melanoma may even help open the door to future advances in cancer care.

ONCEPT Melanoma shows just what is possible when Merial’s experts in recombinant vaccine technology work toward a common goal with leaders in human and veterinary oncology. Dogs with cancer have renewed hope today, and the path to future improvements in cancer treatment for animals and people is a little more clear.

Dr. Robert Menardi, Director, Veterinary Technical Services, Merial

IMPORTANT SAFETY INFORMATION 

ONCEPT Melanoma is intended for dogs with stage II or stage III oral melanoma and for which local disease control has been achieved (negative local lymph nodes or positive lymph nodes that were surgically removed or irradiated). There are no known contraindications for the use of this product in dogs with oral melanoma. In rare instances, administration of vaccines may cause lethargy, fever, and inflammatory or hypersensitivity types of reactions.

Product Availability 

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To find out about specific products and solutions available in your region, explore your local Merial website .

References  

1. Data on file at Merial. Study 05-171. 2009

2. Bergman PJ, et al. Development of a xenogeneic DNA vaccine program for canine malignant melanoma at the Animal Medical Center. Vaccine 2006; 24:4582-4585.

3. Liao JCF, et al. Vaccination with human tyrosinase DNA induces antibody responses in dogs with advanced melanoma. Cancer Immunity 2006; 6:8-17.  

4. Bergman PJ, Wolchok JD. Of Mice and Men (and Dogs): development of a xenogeneic DNA vaccine program for canine malignant melanoma. Cancer Therapy 2008; 6:817­-826.