Researcher eyes vaccines to treat canine skin cancer

NEW YORK — In effort to wipe out canine malignant melanoma (CMM), veterinarians and researchers are working together to target the disease with an emerging weapon in the form of a DNA-based vaccine.

Dr. Philip Bergman of The Animal Medical Center (AMC) in New York believes a melanoma preventive isn't out of the question. This dog was treated at AMC and is now a cancer survivor. The animal hospital specializes in more than 20 areas of medicine and surgery.

The vaccine places human tyrosinase in a canine with CMM, spurring an immune response to the foreign enzyme, prolonging quality and length of life, according to study results.

The Flaherty Comparative Oncology Laboratory at the Animal Medical Center (AMC) and Memorial Sloan-Kettering Cancer Center (MSKCC) combined knowledge on melanomas and the pioneering vaccine to organize the trials that bring the vaccine a step closer to national disclosure.

Philip Bergman, DVM, MS, PhD, head of the Donaldson-Atwood Cancer Clinic at AMC, and Dr. Jedd Wolchok, oncologist at MSKCC, began working on the initial trials in dogs five years ago shortly after Wolchok and Bergman discussed melanoma in dogs and proposed applying the xenogenic tyrosinase to the canine model.

"This vaccine would be nowhere today if it wasn't for Dr. Wolchok," Bergman says. "He spearheaded the project."

Clinical trials performed on the vaccine show the animals' lives are doubled or tripled after receiving treatment.

"Cancer is particularly difficult to treat because the body does not recognize the diseased cells as foreign and does not create a significant immune response against the cancerous cells," Bergman says. "Treatment for dogs was limited to removing the mass, radiation and chemotherapy until Dr. Alan Houghton at Sloan-Kettering had the idea to break the tolerance of the immune system by introducing xenogeneic tyrosinase."

In preliminary trials, dogs' immune systems recognized the foreign tyrosinase and were tricked into attacking its own diseased cells, potentially eliminating the cancer.

The new information on dogs diagnosed with melanoma was enough evidence to initiate the approval process for a United States Department of Agriculture (USDA) licensure trial on the vaccine that continues to be improved by AMC and MSKCC.

If the vaccine receives USDA approval, it will be the first DNA-based vaccine for cancer in animals or humans.

"I see this vaccine most likely being used in an adjuvant situation after the cancerous tumor is surgically removed and/or radiation therapy has been performed," Bergman says. "My long-term goal would be for a preventative vaccine to evolve and be used in veterinary clinics nationally."

Dogs participating in the trials had little or no adverse reaction at the injection site or otherwise due to the vaccine.

"The study helps dogs and humans alike," Bergman says. "The dogs that participated in the trial at AMC all suffered from spontaneous tumors. Since dogs live in the same environment as people and have a competent immune system, it is logical to think dogs are the best model for human malignant melanoma, and the vaccine would work on people the same way that it has for dogs."

In a non-adjuvant trial, nine dogs in stage three or four of CMM received four biweekly injections of human tyrosinase; the longest survivor is still alive more than four years later.

The median survivor time was 389 days. Dogs that receive the combined treatment of removal of the malignant tumor and/or radiation with the vaccine have a median survival time approaching two years.

"Since melanoma is renowned to being extremely resilient against standardized therapies, taking the gene of interest from a different species and putting it in an ailing dog in order to make an immune response. It is one of those things where you say, 'Why didn't I think of that?'" Bergman says.

Down the road

Melanomas contain tyrosinase, which is why the enzyme was targeted for creating the vaccine; however, similar xenogeneic DNA-vaccine approaches will be used on cancers, such as lymphoma and breast cancer, which are expected to be addressed in future studies.

For now, having the melanoma vaccine approved by the USDA would be a great success and a huge step in the right direction for treating cancer, Bergman says.

The study

About 180 dogs have received the vaccine at AMC in different forms during the last four years. Although the breeds studied at AMC vary, breeds that are predisposed to melanomas might be the first to receive the vaccine in a preventive form.

"As technology improves, the profession is basing more vaccines on DNA," Bergman says. "We are also now looking at how the T-cell side of the immune system is stimulated with the vaccine since T-cells are more difficult to work with than the antibody side."

"Equines could also benefit from this vaccine," Bergman says. "Clinical trials would have to be performed on each animal the vaccine would be used on before appropriate labeling would be approved for its use. But that is getting ahead of the main focus: getting approval for use in canines."