In the first phase 1 clinical trial, 21 pet dogs of various breeds with metastatic lung disease due to osteosarcoma or melanoma were treated with the protein interleukin-15 (IL-15).
IL-15 has undergone several human clinical trials because of the toxicity risk associated with the concentrated dose.
“No one has previously used IL-15 as an inhalation therapy in dogs to deliver IL-15 directly to the cancer site.
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Canter explains that we came up with that idea as a means to reduce exposure to the rest of the body, to improve the benefit-risk ratio, to improve the immunostimulatory effects, and to reduce toxicity. count.
“In this study, we used interleukin-15 to repopulate the immune system to make it recognize cancer cells that have evaded the immune system and eliminate them.”
Research shows that amplified levels of IL-15 can stimulate the immune system to protect against certain types of cancer in dogs. IL-15 is one of several types of cytokines — substances that signal and regulate immune system activity.
“As part of our comparative oncology study, we strongly support clinical trials in companion dogs, particularly with regard to whether clinical trials are available,” said Canter, chief of surgery at UC Davis. immunotherapy, as a way to speed up the chair-to-bed translation. Department of Oncology and Co-Director of the Comparative Oncology Training Program at UC Davis.
“The cancers afflicted to dogs, including sarcoma, brain tumors, lymphoma, and melanoma, are extremely similar to cancers that humans develop.”
UC Davis has received a $2 million National Cancer Institute grant to fund a comparative cancer training program to support the next generation of collaborative cancer researchers. cancer in both humans and dogs.
For example, bone tumors and melanomas that develop elsewhere in the body often spread to the lungs, in dogs as well as in people.
In the study conducted between October 2018 and December 2020, dogs inhaled a mist containing IL-15 twice daily. The dosage is increased over time, to help determine not only the effectiveness, but also tolerable and the ceiling to which the toxicity will result.
The dogs had a significant response within 14 days after they started inhaling the IL-15 mist.
Tumors shrank significantly in the two dogs in the study, one of which was in complete remission over a year. The rapidly growing cancer in five other dogs was stable for several months.
“Our overall response rate, the clinical benefit ratio, is close to 40%,” says Canter.
For that and other reasons, additional studies are needed, noted Rebhun, a professor in the Department of Surgery and Radiology of the UC Davis School of Veterinary Medicine.
“The inhaled IL-15 responses we saw in dogs were better than in previous human studies, but the clinical benefit was seen in less than half of the dogs. Use of IL-15 in humans. led to immunological responses that were likely to occur but did not yield a favorable response to the tumor.
This indicates that combining IL-15 with other immunothera- cancer program at the Companion Animal Health Center.
The study found that the therapy was well-tolerated, and even a short two-week course of IL-15 inhalation could provide sustained suppression of metastatic cancer from spreading and progressing.
Both he and Canter note that in a final clinical application, IL-15 will likely not be used as a standalone therapy, but as a booster in combination with other treatments. .
“All of the canine patients in this study had late-stage metastatic cancer and the majority received chemotherapy, radiation therapy, and, in some cases, immunotherapy.
Studies are underway now to see if we can predict which patients might respond to this therapy based on the characteristics of the tumor or the patient’s immune status,” said Rebhun. .
“This can help us identify patients who might respond to this therapy, as well as help us understand how potentially other immunotherapies can be combined to improve response rates.
We are grateful to the extremely dedicated customers who searched for any and all possible care for their pets, chose to enroll them in this study, and even even delivered inhaled IL-15 to their dogs at home — in the hope that it might benefit their dogs, says Rebhun.
Source: Medindia
