The U.S. Department of Agriculture has conditionally licensed a vaccine to treat canine oral melanoma—the first approved therapeutic vaccine for the treatment of cancer in either animals or humans, according to the company that produces it, Merial. The vaccine is indicated for the treatment of dogs with stage II or stage III oral melanoma for which local disease control has been achieved. It has been in the making for some time. Merial has been involved with the research for four to five years, said Bob Nordgren, Ph.D., vice president of biologics research, development and technology acquisition for Merial. The initial research, however, began even further back. Ongoing research into human treatments that was being conducted by Jedd Wolchok, MD, Ph.D., at Memorial Sloan-Kettering Cancer Center in New York City led to collaboration with Philip Bergman, DVM, Ph.D., Dipl. ACVIM (Oncology) at the Animal Medical Center in New York. The collaboration resulted in the canine melanoma vaccine. Dr. Bergman approached Merial to support the research, which helped further develop and refine the vaccine. The vaccine alerts the immune system to the presence of the melanoma tumor protein tyrosinase. The vaccine uses a gene for human tyrosinase inserted into a DNA plasmid. The human tyrosinase produced is different enough from canine tyrosinase that it stimulates an immune response, yet similar enough to the canine tyrosinase that the immune response is directed against melanoma cells. “For Merial and for the field of science, this is groundbreaking,” said Dr. Nordgren. He said that this is the first plasma DNA-based vaccine that will be sold on the market; the first therapeutic vaccine for cancer and the first transdermally administered vaccine in dogs. He said they also had to go through the relationship building with the USDA to understand how to register a therapeutic vaccine. “So there were a lot of firsts that the project team had to manage in this process,” Nordgren said. “For Merial, it’s been very satisfying that we’ve been able to do that as well as open the opportunity for us to advance with other targets.” Currently, the vaccine has only been tested and conditionally approved for use as a therapeutic vaccine. The problem with developing a preventive vaccine is that the population of dogs that might develop cancer of this specific type is small. What Merial plans to do is continue to show the canine melanoma vaccine’s “exquisite safety record,” Nordgren said. In addition, Merial is working to determine how to select a population at risk before considering a prevention program. The experimental data from other species indicates that a prevention application is possible, Nordgren said. Because additional efficacy and safety research will be conducted during the conditional license period, Merial is making the vaccine available only to specialists practicing veterinary oncology, said Robert Menardi, DVM, technical marketing manager for Merial. And because the current licensing is conditional, he said, the vaccine has yet to be formally named. He said that the company intends for the vaccine to be available to a broader practice after the conditional license period. “Canine melanoma is one of the most frustrating and aggressive diseases to treat,” Dr. Menardi said, and the vaccine will provide an additional treatment option. Clinical studies of therapeutic vaccines for oral melanoma conducted by Dr. Bergman have included dogs with oral melanoma that ranged from stage II to stage IV. The enrolled dogs had an estimated life expectancy of one to five months, even after establishing local tumor control with surgery and/or radiation therapy. Dogs that received this vaccine showed increased survival time, according to the studies. At the conclusion of one published study of dogs with advanced disease, patients achieved a median survival time of 389 days. “The development of this vaccine may offer oncologists a new option for treating canine melanoma patients,” said Tim Leard, DVM, Ph.D., director of biologics research and development at Merial. “Beyond surgery, radiation and chemotherapy, oncologists can also consider therapeutic vaccination, which has performed well in extending the lives of dogs with oral melanoma in initial trials.” Nordgren said melanoma was a good first choice for a vaccine because researchers knew action could be taken against it. Other cancers, going on a tumor-specific approach, are more challenging, he said. “We used this as a pathfinder project to make sure we understood what the limitations were and what we might have to do to improve the response,” Nordgren said. “The second approach that we are looking at is doing what we can to boost the host’s response against multiple tumors.” The canine melanoma vaccine is designed to be administered in an initial vaccination series of one 0.4 mL dose every two weeks for a total of four doses. Following the initial series, one booster dose is administered every six months. Merial has also introduced its canine transdermal device, a spring-powered device used to inject the vaccine intramuscularly without a needle. It was developed in conjunction with Bioject, a developer and manufacturer of needle-free drug delivery systems based in Tualatin, Ore. The vaccine will be available by mid-May. For more information, call 888-637-4251, option 3. Merial is continuing its relationship with Memorial Sloan-Kettering Cancer Center and AMC and is looking at other targets, such as lymphoma. <HOME>
