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Pet dogs with cancer play role in testing new injectable chemotherapy drugs

June 08, 2018

By Greg Peters

Remy
After cancer treatment, Remy is as active as ever.

You might not know it by looking at her, but Remy is one lucky dog, and she has one of two new cancer drugs under development in cooperation with The University of Kansas Cancer Center to thank for helping to keep her alive.

The 10-year-old Sheltie arrived in Kansas City after surviving the early part of her life in a puppy mill where she was known only as No 429. Then, after being adopted from the Kansas City Rescue Shelter, she escaped from her new owner and was on her own for 42 days outside of Manhattan during one of the coldest winters in recent memory.

As luck would have it, a man who was using humane animal traps to catch raccoons found Remy when he was inspecting his traps just before leaving on a two-week vacation. His wife recognized Remy from posters that had been circulated, and the dog came back to the rescue shelter where Julie Yoder of Shawnee took her into her home and was able to rehabilitate the severely traumatized dog.

Yoder eventually decided to keep Remy, but last June she noticed an inoperable egg-sized tumor growing on her pet's left front leg. The dog that had survived puppy mills and freezing cold appeared to be in peril. Just when it looked like Remy's luck had run out, her veterinarian remembered hearing about cancer drug trials that were being conducted in pet dogs.

KU researchers have chosen to use pet dogs for several reasons, including the fact that naturally occurring cancers in animals have characteristics more similar to those in humans. The treatments have shown good success in curing or curtailing cancer in some dogs and improving the comfort and quality of life for sicker dogs, who are already in their final days.

Dr. James Humphrey at Johnson County Animal Clinic called HylaPharm, a KU spinout company that has had great success treating cancer in dogs by injecting its original medication, HylaPlat, directly into tumors. And it wasn't long before Remy was accepted as part of a test of one of the two new drugs that are under development - Caninamide and Veresimod.

The treatment protocol called for four shots of Caninamide given two weeks apart, but after just one injection, Remy's tumor showed signs it was dying. Within a few months, the wound had healed so well that Yoder had to examine Remy's legs to remember where the tumor had been.

"I really can't say with any confidence that Remy would be alive today without the treatment." said Yoder. "Surgery wasn't really an option, so being in the HylaPharm study is probably the reason she is cancer-free and here today. They gave me my girl back."

"I'm a people doc, so it's good to know that saving four-legged lives is hopefully one of the steps on the road to saving some two-legged lives," said Daniel Aires, M.D., J.D., co-founder of HylaPharm, a professor in the KU Division of Dermatology and a researcher affiliated with the KU Cancer Center. "Being able to save dogs' lives is a great thing."

Both new drugs are created in a HylaPharm laboratory on West Campus in Lawrence by a team led by co-founder and chief technical officer Laird Forrest, Ph.D., COO, a professor in the Department of Pharmaceutical Chemistry. For both new drugs, the team has been able to repurpose existing products.

Caninamide and Veresimod are designed like their predecessor HylaPlat, so they can be injected directly into cancerous tumors. But unlike HylaPlat, these drugs are part of a new trend in cancer research designed to work with programmed death one (PD1) immune therapies that use a person's own immune system to fight the cancer. The researchers hope that by injecting the medications directly into the tumors, the effects will be more localized and hopefully mesh well with other cancer treatments.

In the case of Caninamide, the team found a way to take an existing antibiotic and make it injectable. Aires said they have put the antibiotic together in a new way, while combining it with other ingredients so that it can be injected directly into cancers and remain in tissue long enough to have a significant benefit.

"It appears to have very few side effects in dogs that have been treated," Aires said. "And we've seen some very good results as well."

Veresimod is part of a family of immune therapy drugs that are not well-suited to be directly injected into tumors. By modifying the molecule, Forrest's team has created a drug that is similar to what existed but is now injectable. Veresimod is part of a class of drugs that can help fight cancer in a variety of ways including attracting immune cells to an area, plus signaling the cells to become active. They can also affect the way proteins in cancer cells present themselves to immune cells. All of which can result in a much more vigorous and strong attack against the cancer.

"Caninamide appears to be a bridge of sorts between HylaPlat and Veresimod," Aires said. "It appears to be directly toxic to cancer cells but not to normal cells, through mechanisms that are not really well-understood. But it also appears to be priming the immune system, so you're kind of getting a two-for-one."

Both drugs are just in their testing infancy, and the team is looking for dogs of almost any sort to take part in the testing. They work with local veterinarians to determine if the dogs and the cancers are suitable for treatments. For families with seriously ill pets it probably won't be a cure, but it could improve the quality of the dog's life.

"We're taking any dog that has a cancer where we think one of our drugs can help, and the family and the veterinarian want to try it," Aires said. "So if all three parties agree, we'll try it. In many cases, we may be able to offer hope for a pet that otherwise has few options. Because natural cancers in dogs are so similar to natural cancers in humans, we are then able to use what we learn to prepare for the day when the treatment is ready for humans. We hope to save pets now and people someday soon."

Choosing which of the three HylaPharm drugs will be used is decided on a case-by-case basis depending on the animal, the cancer and input from the families and veterinarians. The HylaPharm team teaches the veterinarians how to do the injections so they can be done locally. Aires said they also are considering combinations of their drugs to see if that might be more effective.

The path to actually having a commercial product either on the dog or human markets is still uncertain, but they are exploring relatively cheaper and quicker regulatory pathways with expert consultants.

"I get some odd looks when I tell people she was part of a clinical trial at KU Cancer Center," Yoder said. "But I'm quick to point out that she is alive because of it. I don't know what would have happened if not for the trial."

Right now, Aires is just trying to recruit as many dogs as possible into his study, so when the time comes there will be enough data to support moving forward. And because the drugs are still in a trial phase, they are free of charge. Anyone who has a pet dog with cancer can call call 913-213-3028 or email dogs@hylapharm.com   to see about participating in the study.

Last modified: Jul 26, 2018
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