Human and veterinary researchers at UC Davis and other institutions have shown that enhanced natural killer (NK) immune cells, combined with radiation therapy, can be effective against spontaneous osteosarcoma (bone cancer) in dogs. The research showed these NK cells homed in on cancer and reduced metastasis in the treated dogs, offering a potential immunotherapy against solid tumors. The study was published today in the Journal for Immunotherapy of Cancer.
“People have been trying to figure out a way to use NK cells therapeutically to treat cancer patients, but the results have been modest, except in blood cancers,” said Robert Canter, associate professor of Clinical Surgery and first author on the paper. “In this study, we had some preliminary signs of activity. We are especially encouraged that NK cells can be effective against solid tumors.”
While genetically engineered T cells have garnered much attention, they aren’t the only immunotherapy available. NK cells are highly mobile early responders that attack tumors and cells overtaken by viruses. Because their homing mechanisms are less specific than T cells, NKs could potentially hit a wider range of targets. They may also be effective against cancer stem cells: tumor-initiating cells that resist most treatments and can generate recurrent tumors.
“NK cells are always roving around, looking for damaged or transformed cells and killing them,” said William Murphy, professor in the Departments of Dermatology and Internal Medicine and senior author on the paper. “Cancers (and viruses) are constantly evolving. If you’re too specific in your attack, the cancer can evolve in ways so that those cells can’t see it anymore. NK cells are non-specific enough where they’ll usually see it.”
In the study, each canine patient’s NK cells were extracted, expanded and activated. Radiotherapy was administered to enhance the NKs’ ability to destroy tumors. The cells were tested against dog sarcoma cell lines and xenografts and injected directly into the dogs’ bone tumors.
The enhanced NK cells were effective in all three cancer models: killing sarcoma cells in vitro, preventing xenografts from growing and reducing metastasis in the patients. Ten dogs were treated in the study and five showed no signs of metastasis after six months. By comparison, canine osteosarcoma patients that only receive radiation have an 85 percent metastasis rate.
“One dog looked like it was developing lung metastases that ultimately went away,” said Canter. “It’s only one, and it’s anecdotal, but it does suggest our treatment was having an effect.”
Researchers said the research advances cancer therapies for both canines and humans. In October, UC Davis received a $2.5 million National Cancer Institute Moonshot grant to study immunotherapy in dogs. Scientists have long been concerned that mice provide an incomplete model to study therapies that will eventually go into humans. This is especially true for immunotherapies, as lab mice must be immunosuppressed to study human tumors.
Like humans, dogs can spontaneously develop tumors that eventually metastasize. They also live in a human environment.
“The dog model shows proof of concept that we can give cutting-edge immunotherapy to canine cancer patients,” said Murphy. “These dogs can go home, and we can monitor them like a human being.”
While these early results are encouraging, the science has a long journey before helping human patients. For the next step, the researchers want to conduct a larger trial and test different ways to make NK cells better killers.
“The next trial will have more statistical power,” said Canter. “If that shows exciting results, this approach may go to human trials.”
Other author included: Steven K. Grossenbacher, Ian R. Sturgill, Jiwon S. Park, Jesus I. Luna, Michael S. Kent, Arta M. Monjazeb and William T.N. Culp at UC Davis; Jennifer A. Foltz, Dean A. Lee at Nationwide Children’s Hospital; Mingyi Chen at the University of Texas Southwestern Medical Center; and Jaime F. Modiano at the University of Minnesota.
This study received funding from the National Cancer Institute grant (R01 CA189209), the University of California Cancer Research Coordinating Committee (CRR-13-201404), the Society for Surgical Oncology Clinical Investigator Award and the Dr. Mark Starr Family Fund.