By Greg Peters
|Daniel Aires, M.D.|
Cody is an 11-year-old shepherd mix who loves to have his tummy rubbed and his ears scratched. Over the years, Elaine Schindel, a nurse in the radiology department at The University of Kansas Hospital, and her family have grown attached to the golden-haired stray they rescued off the streets.
Elaine and Cody share a special bond well beyond the dog being her family’s beloved pet – both are cancer survivors. Coincidentally, each had their cancer knocked out by different combinations of the same cancer-fighting drug – cisplatin. Elaine is eight years removed from having breast cancer, and Cody was declared cancer free just months after he received a revolutionary injectable cancer-fighting chemotherapy regimen in July that delivers a compound containing cisplatin directly into a tumor.
To create a new drug named HylaPlat, researchers at the University of Kansas and the University of Kansas Medical Center blended cisplatin, a platinum-containing anticancer medication created in the 1970s, with hyaluronan, a polymer that occurs naturally in the human body. In clinical trials, HylaPlat was injected directly into cancerous tumors in dogs, and the KU researchers say the results have shown great promise in treating a variety of cancers. And if the success continues, it could smooth the way for testing in humans.
“We’re really happy with the results,” Schindel said. “I’m a breast cancer survivor, so I want enough dogs to participate in the trial so that it can move on to help humans.”
Dog trials expand almost overnight
The origins of HylaPlat date back as early as 2007 when pharmaceutical chemist Laird Forrest, Ph.D., an associate professor in the KU School of Pharmacy, and his lab team began working on targeted cancer therapies. In 2011, Daniel Aires, M.D., director of dermatology at KU Medical Center, joined Forrest in what would later become HylaPharm, a spinout company located in KU’s Bioscience & Biotechnology Business Center on the Lawrence campus. Forrest is now chief operating officer for HylaPharm and Aires is president and CEO.
“It’s really Laird’s brainchild,” said Aires “For things to succeed, teams have to coalesce around them. We’ve been very lucky to have a good team coalesce around this with a lot of different talents to help push it forward.”
The team used hyaluronan to create HylaPlat because it enables a non-destructive local injection and sticks well to cancer cells, allowing for an efficient uptake of cisplatin into the tumor cells. And because the compound molecule of hyaluronan and cisplatin is only 20 nanometers in size, after doing its work in the tumor, HylaPlat drains easily into the lymph nodes, delivering a high dose of chemotherapy to any cancer cells there.
In the initial clinical trial starting in 2012, seven large-breed dogs with small forms of oral cancer received what researchers determined to be a “good” formulation of the chemotherapy. They used pet dogs suffering with actual cancers as opposed to lab animals for a variety of reasons, one of which is the limits that model cancers pose for researchers. Lab cancers have to be grown carefully under strict conditions, while real-world cancers, Aires explained, are made much hardier, have ways to evade the body’s immune system, and are made up of multiple kinds of different cells that make them hard to kill.
Of those first seven dogs, the cancer in three disappeared, and two others showed signs of partial remission or slowing of the disease. By 2013, the researchers knew they were onto something, but things progressed slowly until last summer when the treatment was featured on a local television news story.
Suddenly the floodgates were open, and pet owners with dogs suffering from all forms of cancer wanted in the trial. The demand was so great that the team shifted gears, lifting the restrictions on the size of the dogs and types of cancers being tested. Because of the overwhelming demand, veterinarians were trained to use the treatment for cancers all over the bodies of dogs, including muscle and bone tumors, sarcomas, melanomas and lymphoma.
One of those pet owners was Schindel, who saw the news video posted on Facebook and called Aires. Cody’s family had noticed a lump growing on his right hind foot earlier this year. He’d had fatty tumors removed before, but a biopsy by the family veterinarian suggested this was cancer. Schindel and her family worried about Cody’s quality of life if he had to have his back leg removed.
Cody received his HylaPlat injection on July 15. Within weeks he was back to being himself, although his veterinarian is still monitoring Cody’s liver enzymes, which were elevated after the injection. But except for a small scar on his right back paw where the cancer was removed and having his belly shaved for follow-up ultrasounds, you’d never know he’d had cancer. Because of dogs like Cody participating in the trial, man’s best friend might play a key role in changing the way doctors treat cancers in humans.
From dogs to humans
While success in dogs is a start, the KU team knows the road to approval for treating humans is long and difficult, requiring a lot of resources. That said, Aires is optimistic that human trials could begin in the next two or three years. Currently, the team is preparing for safety trials, which set the stage for applying for investigational new drug (IND) status, a prerequisite for starting human trials.
“We think we’re ready to start that process,” Aires said. “Based on the results we’re seeing from our latest formulation, the balance of safety and effectiveness seems to be good. We think this will be valuable in treating human cancers.”
While researchers are cautiously optimistic about the chances that injectable targeted chemotherapy can work in humans, they know it’s a long way from receiving Food and Drug Administration approval. Getting a canine version of HylaPlat to market, however, appears to be on the fast track, which should come as a delight to pet owners and the drug’s creators.
“It will be the best feeling knowing that we’ve actually been able to take something from the laboratory out into a little spinout company and then see it actually get out into the world,” said Aires. “We don’t want to count our chickens before they hatch. But there’s a tremendous excitement and a feeling that you want to build this thing and see it start to work and to change lives.”