A protein that the body naturally produces could become an important new immunotherapy drug in the cache of cancer-fighting tools available to oncologists. UC Davis cancer researchers for both companion dogs and humans joined scientists from other institutions to study a new approach that triggers the body’s defense mechanisms, its T-cells and natural killer (NK) cells, to respond and destroy cancer.

Surgical oncologist Robert J. Canter with UC Davis Comprehensive Cancer Center and canine oncologist Robert B. Rebhun with the UC Davis School of Veterinary Medicine are corresponding authors for a study just published in the Journal for ImmunoTherapy of Cancer.

In the first-of-its-kind Phase 1 clinical trial, 21 pet dogs of various breeds that had metastatic lung disease resulting from osteosarcoma or melanoma were treated with protein interleukin-15 (IL-15). Although previously recognized for immunotherapy properties, IL-15 has undergone few human clinical trials because of toxicity risks associated with concentrated doses.

“No one previously had administered IL-15 as an inhaled treatment in dogs to deliver it directly to the site of the cancer. We came up with that idea as a means of reducing exposure to the rest of the body, in order to improve the benefit-risk ratio, to improve the immune stimulating effects, and to reduce toxicity,” Canter explained. “In this study, we used interleukin-15 to reinvigorate the immune system to make it recognize the cancer cells that had evaded the immune system and eliminate them.”

The research shows that amplified concentrations of IL-15 can stimulate immune system defenses against some types of cancers in dogs. IL-15 is one of several types of cytokines — substances that have signaling and regulating functions in immune system activity.

“As part of our comparative oncology research, we are strong advocates of clinical trials in companion dogs, especially for immunotherapy, as a way to speed bench-to-bedside translation,” said Canter, who is chief of the UC Davis Division of Surgical Oncology and co-director of the comparative oncology training program at UC Davis. “The cancers that afflict dogs, including sarcomas, brain tumors, lymphoma and melanoma, are incredibly similar to cancers that humans develop.”

UC Davis received a $2 million National Cancer Institute grant to fund the comparative oncology training program to support the next generation of oncology researchers collaborating on curing cancer in both humans and dogs. For instance, osteosarcoma and melanoma that develop elsewhere in the body commonly spread to the lung, in dogs as well as humans.

Source: Read Full Article