At the third International Cancer Immunotherapy Conference in Frankfurt last week, Ellen Puré may have seemed a bit out of place as professor and director at the University of Pennsylvania School of Veterinary Medicine. This was, after all, a scientific conference focused on the latest research in the red-hot field of immuno-oncology, the quest to engage the human immune system in the fight against cancer. But as Puré explained to reporters attending the conference, it’s not just people who are participating in clinical trials of engineered CAR-T cells, cancer-killing viruses and other immune-boosting treatments — and it’s not just human patients who are benefiting from this relatively new branch of oncology research.
“Early on, the hit rate [with immuno-oncology treatments] was very low, because we were throwing cancer cells in a test tube and throwing drugs at them and asking what worked. Then we went into mice and then patients,” said Puré, a biomedical scientist by training. “But the systems were artificial. They didn’t relate to humans. We have spontaneous tumors in larger animals, like cats and dogs, that are much more similar to humans.” The conference was sponsored by several organizations, including the Cancer Research Institute and the American Association for Cancer Research.
The idea of involving pets that develop cancer naturally in clinical trials of new treatments is gaining steam in cancer research. Part of the reason has to do with the immune system itself. Rodents that are traditionally used in cancer research are often “immunodeficient” by design, meaning they are engineered to have fewer of the critical immune cells known as T cells than they would normally have. What’s more, they don’t develop cancer on their own, so they have to be given the disease, perhaps by implanting human tumors under their skin. This may be why so few treatments that cure mice end up working in people.
Pet dogs (and cats) that live in our homes develop many of the same cancers people do, including osteosarcoma, breast cancer and lymphoma. Therefore, they offer an opportunity to preview immune-boosting treatments in species that are very much like us, both in their genetic makeup and in how they experience cancer.
The National Cancer Institute (NCI) is one of the supporters of this research, and last year it solicited funding applications from scientists interested in performing clinical trials of immuno-oncology treatments in dogs. In a briefing document, the NCI provided several examples of similarities between the human and dog immune systems. For example, dogs have genes for PD-1 and PD-L1, the immune “checkpoints” that normally prevent the immune system from recognizing and attacking cancer. PD-1 inhibitors such as
However, PD-1 inhibitors don’t work in many patients. Figuring out why that is — and fixing it — is a challenge that dogs could help overcome, the NCI suggested.
Dogs are already helping improve the design of human immuno-oncology clinical trials. For example, a paper published in 2015 described a trial in 11 pet dogs of interleukin (IL)-12, a protein that helps activate tumor-hunting T cells. The results were mixed: Some dogs didn’t respond at all, some had partial responses, and one responded well for a full nine months before its cancer progressed. The results were used to enhance the design of a human clinical trial in which IL-12 in being combined with a PD-L1 inhibitor. The German pharma company Merck KGaA is sponsoring that trial.
But for the idea of enlisting pets in immuno-oncology research to really take hold, there will need to be more buy-in from Big Pharma. There hasn’t been so far, but that’s starting to change, says Ben Lewis, a veterinary student at Penn who founded The One Health Company, which matches dogs with clinical trials meant to yield new treatments for both people and pets. “There are only a handful of companies doing this, but I’m seeing incredible traction,” Lewis says. “Companies are coming to us with trial ideas for everything from universal cancer vaccines to looking at biomarkers to predict which animals will and won’t respond to a given therapy.”
There are still hurdles to be overcome, to be sure. “Canines provide us an opportunity to prove out immunotherapies in a more relevant model — spontaneously developing cancer — but we also need to do a little more mapping of the canine immune system to really fully understand how it compares to the human immune system,” says Ulrike Szalay, founder and executive director of the Canines-n-Kids Foundation, which is raising money to fund oncology research in pet dogs that has the potential to yield treatments for people. “So there’s still some work to be done, but I think the opportunity is clear.”
The field of immuno-oncology has advanced rapidly in recent years, with the FDA approvals of checkpoint inhibitors, and most recently of Kymriah, the CAR-T treatment from Novartis that involves removing T cells from leukemia patients and then engineering the cells to recognize and kill their cancers.
Those successes have intensified the demand for even more innovation in immuno-oncology, said Penn’s Puré during the recent immunotherapy conference in Germany. Trying those new therapies in pets that have cancer will allow scientists to “make sure you have that rationale to jump into the clinic,” she said. “We need to learn why it works and also why it doesn’t work, so we can go back and improve it.”
