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Tuesday, August 9, 2022

New immunotherapy for dogs can help researchers understand lung cancer therapies

UC Davis researchers uncover and compare potential benefits of dog immunotherapies

 

By MONICA MANMADKAR — science@theaggie.org

 

Comparative oncology is one of five research programs within the UC Davis Comprehensive Cancer Center, which has a long history of supporting collaborative comparative and translational research between the medical and veterinary schools. This is in part because many models to study cancer require the induction of tumors into animals that have compromised immune systems, which can limit researchers’ ability to study novel immunotherapies for cancer.  

Naturally-occurring cancer is the leading cause of death in domesticated dogs, and several of these cancers are clinically, molecularly and genetically similar to cancers that occur in humans. Because dogs naturally develop these cancers in the presence of an intact immune system, studying novel immunotherapy strategies in dogs has the potential to help both dogs and people.  

  Surgical oncologist Robert J. Canter at UC Davis Comprehensive Cancer Center and canine oncologist Robert B. Rebhun at the UC Davis School of Veterinary Medicine are the corresponding authors of a study on immunotherapy for dogs that is helping them understand lung cancer therapies that could potentially be adapted for human use in the future as well. 

“Cancers that dogs get [are] very similar to the cancers that people get, so dogs are an innovative [model] to develop and translate novel cancer therapies — especially for immunotherapy, which is hard to study in mice and hard to test in humans because clinical trials are time-consuming and expensive,” Canter said. “We had an idea that delivering immunotherapy via a breathing treatment would overcome some of the barriers to success of this specific immunotherapy approach previously.”

The key results of the study were established from the first published trial which determined the safe dose of interleukin-15, an inhaled protein that serves to activate the immune system to fight cancer. Because it is inhaled directly to the lung, it is aimed at metastatic tumors that spread to the lungs. 

The goals of the study were to establish protein’s safety and determine if it helped to shrink any of the tumors. The researchers found that this treatment was well tolerated and, importantly, some of the dogs experienced durable responses despite only receiving a short two-week-long therapy.

While interleukin-15 has been shown to activate the immune system in human patients with cancer, when injected by itself, it has not proven effective.  

“Our trial showed that delivery of inhaled [interleukin-15] directly to the lungs of dogs could lead to durable responses,” Rebhun said. “However, based on the results from human trials and because less than half of the dogs appeared to benefit from this therapy, it is believed that [the protein] may be more effective when combined with other immunotherapy strategies.”

Canter also explained that the study found that the approach was well-tolerated and easy to administer with acceptable side effects. He said that since the immune system was activated in response to the treatments, the treatments were likely having at least some of the intended effects.

Since not all of the tumors responded, the researchers hope that ongoing studies will help identify whether patient- or tumor-specific factors could predict whether an individual patient, either dog or human, might be likely to benefit from this therapy. These results could also help guide the researchers in selecting different therapies for lung cancer, and ways of testing these therapies, in the future.

 

Written by: Monica Manmadkar — science@theaggie.org