A Round of “uh-Paws” for Dr. Wolchok

CRI Scientific Advisory Council associate director Jedd Wolchok is a recipient of the 2013 Puccini Foundation “Shared Cancer, Shared Cures Visionary Award.” The award recognizes Wolchok’s contribution to the development of the first USDA-approved vaccine for the treatment of melanoma in dogs. CRI chief executive officer and director of scientific affairs Jill O’Donnell-Tormey presented the award to Wolchok at the Puccini Foundation’s inaugural awards celebration, held on Monday October 28, 2013, in NYC. Wolchok was one of three individuals honored that night for their contributions to the field of comparative oncology; the other two were Dr. Philip Bergman of the Katonah-Bedford Veterinary Center and David Petrie of the Blue Buffalo pet food company.

“Do Dogs Get Melanoma?”

The work for which Wolchok was honored came out of a dinner party conversation back in 2000. While sipping a glass of wine, someone posed the question to Wolchok, a medical oncologist at Sloan-Kettering: “Do dogs get melanoma?”

It turns out they do, and the cancer in man’s best friend is quite similar to the melanoma that people get: spontaneous, aggressive, and deadly.

Wolchok didn’t know much about how melanoma in dogs was treated, but the question got him thinking. Would dogs respond to immunotherapy? And if they did, could this help people suffering from the same disease? 

For a number of years, Wolchok had been conducting research on immunotherapies for patients with metastatic melanoma. There aren’t a lot effective treatments for this aggressive disease—it’s resistant to most chemotherapy—and so the need for new approaches is great. One approach that he and other researchers have considered is a cancer vaccine.

Most vaccines in use today are for infectious diseases. The idea behind a vaccine is simple: by exposing the immune system to a tell-tale piece of pathogen, the immune system is alerted to danger and mounts a specific attack against invaders that have this trait. It also forms a memory of the attackers, should they try again.

Creating a vaccine specific to cancer is trickier since cancer cells are really just altered versions of one’s own cells, and so they are not as easily recognized as foreign or dangerous—with one important exception. Cancer cells from a different species can be easily recognized by the immune system and rejected. That’s because the proteins from different species have slightly different sequences, and the immune system can easily detect these differences. Proteins from another species are referred to as “xenogenic” (from the Greek “xeno—,” meaning strange or other, and “—genic,” meaning produced or cause by).

In 1999, Wolchok received a grant from CRI to conduct a clinical trial of a xenogenic vaccine in humans with melanoma. The vaccine consisted of a piece of DNA from a mouse transferred into a bacterial “cloning vector,” which would then be injected under the skin. (A cloning vector is essentially a tiny molecular machine for churning out proteins.) The DNA vector makes a protein called tyrosinase, which is found at much higher levels on melanoma cells than regular body cells. The idea was that the mouse protein would be different enough from human tyrosinase to trigger an immune response, yet similar enough to direct the immune response against melanoma cells.

The idea made good scientific sense, but the trial was stalled in “the necessary but voluminous paperwork permissions process for testing in humans,” Wolchok says. That’s when he got to thinking about another cross-species interaction—that between dogs and humans. What if he designed a similar vaccine for dogs, but with human DNA instead—would it be easier to get approval for this study? And would it work?

To explore this possibility, Wolchok teamed up with a colleague, a veterinarian named Philip Bergman at the Donaldson-Atwood Cancer Clinic of the Animal Medical Center in NYC, who was already conducting clinical trials of experimental medicines for dogs with cancer. A partnership was born and, "within four months we were testing the vaccine on dogs with late-stage cancer," Bergman recalled.

From April 2000 to June 2007, approximately 500 dogs with melanoma were treated with the DNA vaccine. The results? Compared to historical controls of dogs treated with surgery alone, the treatment of surgery plus vaccine significantly improved survival times. Based on these encouraging data, the USDA granted preliminary approval for the vaccine in 2007, and final approval in 2010. The DNA-based vaccine for canine melanoma was the first ever therapeutic vaccine approved for cancer—in either dogs or humans. The vaccine is now marketed and sold as ONCEPT™ (Merial).

In addition to lending a helping paw to man’s best friend, the work that Wolchok and Bergman did on the canine vaccine was also influential in creating a more favorable climate of opinion for human immunotherapies. "There’s no question that the success of the animal trials did a lot to speed up the approval process of the human trials," says Wolchok.

Comparative oncology continues to be a thriving field of inquiry, one that the Puccini Foundation seeks to support. Founded in 2007 by Linda Cohen Wassong, the Puccini Foundation is a nonprofit organization devoted to increasing awareness and raising money for comparative oncology research. Wassong says she was inspired to create the organization after her Cocker Spaniel, Puccini, was diagnosed with melanoma in 2006. Puccini was one of the dogs that participated in the Wolchok-Bergman trial. Wassong’s hope for the Foundation is that it will help lead to shared cancer cures, for both pets and people.

That Wolchok received such a big, wet smooch from a canine-friendly organization is a bit ironic. Until quite recently, Wolchok was not a big fan of dogs. That’s because, as O’Donnell-Tormey mentioned in her introduction, he was bitten by one back in high school. But Wolchok has since come around to embrace the bond that links dogs and people. He says he’s gratified to know that his work is helping two species who mean so much to each other.

This isn’t the first time that CRI has taken an interest in non-human animal cancers. The Donaldson-Atwood Cancer Clinic, where Bergman worked at the time, owes its existence in part to CRI. Back in the 1970s, CRI medical director Lloyd Old and founding director Helen Coley Nauts were instrumental in establishing the animal cancer clinic, with the understanding that lessons learned in non-human animals might apply to people. Just another example of CRI’s long-range view, and the creative way it has supported and nurtured the field of immunotherapy, getting us to where we are today.   

For more about the Puccini's inaugural award event, you can read the news release here.