UC Davis has received its first National Cancer Institute (NCI) Moonshot grant ̶ $2.5 million over five years ̶ to explore immunotherapy treatments for dogs who develop melanoma and osteosarcoma and that may one day benefit humans, as well.
“These are two cancers that dogs get which are similar to human cancers, and we need new therapies for both of them,” said Robert Canter, a surgical oncologist at the UC Davis Comprehensive Cancer Center and the study co-principal investigator. “Both of these diseases often go right to the lungs and have extremely high mortality rates.”
Canter and co-principal investigator Robert Rebhun, a veterinary oncologist and researcher at the School of Veterinary Medicine, will use the grant to expand earlier work that demonstrated that natural killer cells, when combined with radiation therapy, can be activated to control cancer growth. The research team will conduct three clinical trials.
“We have been a leader in canine immunotherapy,” said Canter. “We were the first in the country to do a clinical trial with natural killer cells in dogs. We are looking for ways to optimize making them effective in dogs so we can bring them to people.”
Rebhun added that cancer is the leading cause of death in pet dogs, and that dogs with naturally occurring cancers are good research animal models because unlike many mouse models, dogs have fully functional immune systems.
“Through Moonshot, the NCI is betting that canine studies will directly translate, inform and improve immunotherapy for human cancer patients,” he said. “This is a ‘win-win’ in that we can investigate promising immunotherapies for pet dogs with cancer that otherwise may be out of treatment options.”
Natural killer cells are white blood cells of the immune system adept at killing cells infected with viruses and cancer cells in the blood. In the new study, Canter and Rebhun will combine the natural killer cells with cytokines, which are proteins released by immune system cells that help regulate immune response.
The researchers will first isolate the natural killer cells from canine patient blood samples then expand them in the laboratory. One of the main goals of the new research is to reinfuse the dog’s natural killer cells in combination with human IL15, a cytokine known to activate natural killer cells in both dogs and people. The hope is that the addition of cytokines will help keep the natural killer cells active and primed to attack cancer cells in the body.
The first two trials will be in dogs whose disease has spread to other organs. In the first trial, the cytokines will be injected, and in the second trial the cytokines will be inhaled to optimize their effect against tumors in the lungs. For the third trial, the inhaled cytokines will be given to patients whose osteosarcomas have not advanced to determine if the treatment can prevent metastases. A total of 70 dogs will participate in the trials.
In addition to determining whether the treatments are effective, Canter said they will also evaluate treatment toxicity to make sure it is tolerable.
“We also will be doing sequencing to see if our treatment is impacting the immune response and tumors in terms of what antigens are being targeted by the immune system,” Canter said.
Rebhun stressed that while the trials aim to yield discoveries that can benefit people, the dogs are not experimental animals, but patients and beloved family members.
“Patient care and quality of life remain paramount, and we truly hope these therapies can also help our canine patients,” he said.
In addition to Canter and Rebhun, investigators include Arta Monjazeb, Michael Kent , William Murphy, Ellen Sparger, Titus Brown, Susan Stewart and William Culp.