MU oncology researchers have helped develop a new precision medicine that fights osteosarcoma, a type of bone cancer common in dogs.
Jeffrey Bryan, veterinary oncologist and the director of the Comparative Oncology, Radiobiology and Epigenetics Laboratory, helped to design the clinical trial and lead the trial efforts. The researchers partnered with ELIAS Animal Health to carry out research into combating the disease.
“It was sponsored by the ELIAS Animal Health company,” Bryan said. “Their chief scientist Gary Wood developed this immunotherapy approach to treating cancer, and he has tested it previously in human clinical trials as well. They did the work of creating the tumor vaccines.”
The idea for this research was brought to the attention of Carolyn Henry, dean of the College of Veterinary Medicine, a few years ago by ELIAS CEO Tammie Wahaus and director Gary Wood.
“The osteosarcoma clinical trial is the culmination of a collaboration that started many years ago when I was introduced to Tammie Wahaus and Gary Wood, then of TVAX Biomedical, at a scientific meeting in Kansas City,” Henry said in an email. “They were interested in the animal health market for new cancer therapies, and we were collectively interested in finding better, less toxic treatment options for dogs with cancer.”
Though osteosarcoma is most prevalent in dogs, there are rare cases of humans with the disease.
“About 660 to 800 kids get osteosarcoma in the whole country every year,” Bryan said. “The horrible tragedy of that cancer in particular is that it tends to strike preteens and teens. It’s very damaging to the limb. It’s about 10 times as common in dogs. We see over 10,000 cases in dogs in the United States each year, equally as devastating.”
Brian Flesner, assistant professor of oncology and a co-investigator in the study, noted that osteosarcoma’s high rate of metastasis, or developing another growth in a different part of the body, makes the disease especially difficult to combat.
“This tumor is highly aggressive and has about a 90 percent metastatic rate,” Flesner said. “If you get local control, whether that’s with a definitive surgery or some other means of removing the tumor, 90 percent of dogs will fail distantly. It’ll spread mainly to their lungs. The exciting part of this trial was it was the first one that didn’t involve chemotherapy and showed extended survival in dogs.”
The first step in treating dogs with osteosarcoma is amputating the limb with the tumor since it has been so badly damaged, Bryan said. From there, the researchers harvest tumor cells and send them to ELIAS, where a vaccine is made from the cells.
“The concept of precision medicine is that you give every patient a treatment that will work for that patient at the right time that they need it, causing as little toxicity as possible,” Bryan said. “We’re using their own tumor cells to make the immune system wake up and pay attention to the cancer, so that’s as precise as you can get. Then we’re using their own immune cells to further that immune attack on the cancer and hopefully eliminate the cancer wherever it hides.”
In contrast to recent MU research, where three dogs survived out of a group of 30 that received chemotherapy to treat the disease, the immunotherapy research has seen five out of 10 participating dogs survive, a significant increase, Bryan said.
“They do not have active cancer that we can find in their body, but we’ll just have to see what the years bring,” Bryan said. “Most usually, following amputation and chemotherapy, we expect survival times in the nine months to a year range, and the fact that these dogs are still alive and well with no evidence of tumor 18 months down the road is a really impressive outcome.”
This success rate achieved what Flesner said the study aimed to do: to show the safety and efficacy of the precision medicine approach.
“The big goal was to show that it is safe, that we can actually collect dogs’ white blood cells and give them back to them,” Flesner said. “The other part of it, which needs to be proven by a much bigger study, is efficacy. I know that’s what everyone wants to know is how well does it work, but first we had to show that it was safe and that we could actually do what we wanted to do. I think we showed that very well.”
Since osteosarcoma is seen in both dogs and humans, the researchers have a chance to develop immunotherapy methods that may be applied to humans in the future as well.
“The opportunity that we have in it being so common in dogs is that we can test approaches in dogs and find out relatively quickly whether those approaches are beneficial,” Bryan said. “If we can find beneficial applications of therapy, either immunotherapy or a new chemotherapy, then it’s a question of identifying whether that’s an appropriate approach to try to translate back into kids who have osteosarcoma.”
Henry also expects that research such as this will help develop human treatments to disease.
“Companion animals are affected by most medical illnesses that affect people, so the two medical fields can learn a lot from each other,” Henry said in an email. “We anticipate that many treatments we study will become commercially available in the years to come—both for animals and for human cancer patients.”
Flesner, who has worked as principal investigator at MU for three osteosarcoma trials, all using chemotherapy rather than immunotherapy, said that the precision medicine approach may result in avoiding many of chemotherapy’s side effects.
“For so long, it has just been chemotherapy to try and kill anything that is rapidly dividing within the body,” Flesner said. “The issue with that is you have all kinds of side effects with other rapidly dividing tissues in your body like your bone marrow and your gut. If we could replace some of those less precise, more generic treatments like chemotherapy with individual precision treatments, we could maybe spare more side effects and also have a much more focused and better response for dogs and people.”
As far as applications of this research go, the precision therapy is now available commercially at the ELIAS centers.
“Because this uses all the patient’s own cells, this can be applied immediately,” Bryan said. “The [U.S. Department of Agriculture] regulates what we call autologous products, and they have already said that the company can offer this on a commercial basis as an experimental therapy for the time being. Anybody whose dog develops bone cancer who can get to one of these centers could purchase this treatment for their dog immediately.”
For Bryan, this rapid turnaround time is unique in his career.
“This is the first time I’ve gotten to see a process go from concept all the way to commercial application,” Bryan said. “That’s a really rewarding sense to feel that we had a large role in making something available that is going to benefit a lot of dogs, and down the road, I think a lot of kids too.”
_Edited by Emily Wolf | ewolf@themaneater.com_