New immunotherapy may help combat canine cancer

According to breakthrough research published in the Journal for ImmunoTherapy of Cancer,¹ a protein the body naturally produces—interleukin-15 (IL-15)—may serve as a new immunotherapy drug to help combat canine and human cancer.

In the Phase 1 clinical trial, 21 dogs of different breeds with metastatic lung disease from osteosarcoma or melanoma were treated with IL-15. The research demonstrated that amplified concentrations of IL-15 can stimulate immune system defenses against some forms of canine cancer as it is one of several types of cytokines.²

“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,” said Robert J. Canter, MD, professor for surgical oncology at the UC Davis Comprehensive Cancer Center, in a university release.²

“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,” added Canter, who is also 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.” 

Methodology

The study was conducted between October 2018 and December 2020, and dogs inhaled a mist containing IL-15 twice daily.¹ Doses were increased over time, and dogs experienced noteworthy responses within 2 weeks after they started inhaling the IL-15 mist.

For 2 dogs in the study, tumors shrank dramatically, including one that went into complete remission for over a year. Cancer that had been growing quickly in 5 other dogs stabilized for a few months. “Our overall response rate, the clinical benefit rate, was close to 40%,” Canter expressed, in the release.²

Thus, further research is needed commented Robert Rebhun, DVM, PhD, a professor at the UC Davis School of Veterinary Medicine’s Department of Surgical and Radiological Sciences. Rebhun also holds the Maxine Adler Endowed Chair in Oncology and is the associate director of the cancer program in the Center for Companion Animal Health.

“The inhaled IL-15 responses that we’ve seen in dogs are better than prior human studies, but clinical benefit is seen in less than half of the dogs. Using IL-15 in people has led to potentially favorable immune responses but has not yielded good tumor responses. This indicates that combining IL-15 with other immunotherapies may result in additive or synergistic responses,” said Rebhun.²

Notable results

According to Rebhun,² the research revealed 2 significant findings: the therapy was well tolerated, and even just a 2-week course of inhaled IL-15 could result in sustained suppression of advanced and diffuse metastatic cancer. Rebhun along with Canter agreed that in future clinical application, IL-15 would likely be used in a multimodal approach coupled with other treatments.

“All of the canine patients in this study had advanced metastatic cancer, and the majority already had received prior chemotherapy, radiation therapy and, in some cases, immunotherapy. Studies are ongoing now to see whether we can predict which patients might respond to this therapy based on properties of the tumor or the patient’s immune status,” Rebhun said.²

“This may help us identify patients that might respond to this therapy, as well as help us understand how to potentially combine other immunotherapies to improve response rates,” he added. “We are grateful to the extremely dedicated clients who sought any and all possible care for their pets, elected to enroll them in this study, and even delivered the inhaled IL-15 to their dogs at home—in hopes that it could benefit their dog, other dogs, or possibly even people with advanced metastatic cancer.”

The National Institutes of Health supplied the recombinant IL-15 as part of the funding for the study. The research was supported in part by National Institutes of Health and the National Cancer Institute.²

References

1. Rebhun RB, York D, et al. Inhaled recombinant human IL-15 in dogs with naturally occurring pulmonary metastases from osteosarcoma or melanoma: a phase 1 study of clinical activity and correlates of response. J Immunother Cancer. 2022 June;10(6):1-15. doi: 10.1136/jitc-2022-004493.
2. Dogs inhale new immunotherapy to fight lung cancer. News release. UC Davis Health. June 10, 2022. Accessed June 17, 2022. https://health.ucdavis.edu/news/headlines/dogs-inhale-new-immunotherapy-to-fight-lung-cancer-/2022/06