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World’s largest canine cancer vaccine trial begins

May 8, 2019

5-year study to examine any beneficial effects on 800 dogs

Meet Trilly: The black-and-tan, floppy-eared, 9-year-old Gordon setter may have just made medical history by receiving a shot that may contain the very first vaccine intended to prevent cancer.

“First one. We did it!” said Arizona State University scientist Stephen Johnston, a professor in the School of Life Sciences and director of the Biodesign Center for Innovations in Medicine.

For Johnston, the moment was the culmination of a 12-year, high-risk, high-reward quest to reshape the way we approach treating cancer, by preventing cancer before it can start. “If this can work in dogs — and that’s a big if — then we believe it can work in people too,” said Johnston, who developed the vaccine with his team at the ASU Biodesign Institute’s Center for Innovations in Medicine.

Stephen Johnston

That’s because, just as in people, cancer is the No. 1 cause of illness and death in older dogs. One out of every three dogs are affected by cancer, and 6 million new canine cancer cases are diagnosed every year.

With her owner Caroline Randy by her side, Trilly received her vaccine shot at the University of Wisconsin-Madison School of Veterinary Medicine, which is participating in the Vaccination Against Canine Cancer study. Next in line was Norton, a 9-year-old rat terrier mix.

As part of the study, the dogs were given either a vaccine or placebo (neither the dog owners nor the scientists know which) and will be monitored during the study. More than 800 dogs will be enrolled, making it the largest clinical trial conducted to date for canine cancer. The study was made possible by a $6 million grant Johnston received from the Open Philanthropy Project. The UW School of Veterinary Medicine is one of three participating institutions, along with Colorado State University and University of California, Davis.

“We’re testing a totally novel way of creating an anticancer immune response,” said David Vail, a professor and board-certified oncologist at the UW School of Veterinary Medicine. “The holy grail would be to prevent cancer as opposed to waiting for it to start and then treating it.”

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The anticancer vaccine being tested is made up of a proprietary cocktail developed by Johnston's ASU team that targets approximately 30 abnormal proteins found on the surface of cancer cells. These proteins, a result of improperly coded RNA — so-called frame-shift mutations — are generally only found in patients with cancer (in both dogs and people).

By injecting this cluster of proteins into healthy patients, along with a substance that stimulates an immune response, researchers believe the vaccine could serve as a universal defender against cancer by “turning on” the immune system to recognize and defeat cancer.

The vaccine can target several cancers common to dogs, including lymphoma, a cancer of the lymphatic system; osteosarcoma, or bone cancer; hemangiosarcoma, a deadly cancer that originates in the blood vessels and is almost exclusive to dogs; and mastocytomas, or mast cell tumors.

A woman holds a dog in a lab

Veterinary technician Abbey Ace holds her dog Norton, a 9-year-old rat terrier mix, after he received one of the first shots in the Vaccination Against Canine Cancer Study. Photo by Meghan Lepisto/UW-Madison

The trial is slated to run over five years. Cancer-free, healthy dogs between the ages of 6 and 10 will be randomized to receive either a series of the investigational vaccine or placebo vaccines. Healthy, middle-aged pet dogs will be enrolled, continuing to live their normal lives at home and receiving biannual exams with a complete clinical pathology workup. 

Dogs will be randomly chosen to receive either the vaccine or a mock version. Dogs receiving the mock vaccine are expected to develop cancer at normal rates. The experiment will determine whether the test vaccine can prevent cancers.

Two sets of vaccines will be given every two weeks, for a total of four treatments, and then annually. Researchers have not observed any side effects other than those typical to any vaccine in mice or dogs to date, such as moderate local pain or swelling at the site of injection, but the study will characterize any unanticipated adverse reactions in the larger study population.

Participating dogs will live at home and be checked two to three times yearly for five years after enrollment to monitor them for the development of any cancers.

“We should know as soon as two years from now whether or not we see the vaccine is having an effect,” said Johnston.

Their medical care will be covered by the study, through funding by the grant from Open Philanthropy. It is also supported by Calviri Inc., a company Johnston started to commercialize the vaccine if it is effective.

If the trial is successful, Johnston’s company, Calviri, plans to create a cancer vaccine for humans. Johnston said they have the technology to make the human vaccine right now, but even optimistically it would be five to 10 years before human use.

“This is probably the only approach to this type of vaccine, so we feel we have to try it,” said Johnston. “The implications of success would be quite large — for dogs and people.”

Top photo: Trilly, a 9-year-old Gordon setter, received the very first shot in the Vaccination Against Canine Cancer Study, a five-year clinical trial to evaluate a vaccine strategy for the prevention, rather than the treatment, of cancer in dogs. With more than 800 patients enrolled, it is the largest clinical trial conducted to date across the history of veterinary medicine. Photo by Meghan Lepisto/UW-Madison

Joe Caspermeyer

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ASU awarded $6.4M grant to test preventive cancer vaccine for dogs

ASU to lead biggest cancer intervention trial in dogs ever conducted.
ASU team wants to eventually make leap from cancer research in dogs to humans.
January 3, 2018

Grant will support the largest interventional canine clinical trial ever conducted

Editor's note: This story is being highlighted in ASU Now's year in review. Read more top stories from 2018 here.

The Open Philanthropy Project awarded a multi-year grant of $6,421,402 to Stephen Albert Johnston at Arizona State University to support the largest interventional canine clinical trial ever conducted. The trial will assess the effectiveness of a unique vaccine in preventing any type of cancer in dogs. 

The trial will enroll at least 800 owners’ pets to test the efficacy of a novel vaccine to prevent cancer.

“Our goal has always been, that if this is possible, we should at least try it,” said Johnston, who directs the Biodesign Center for Innovations in Medicine and is a professor in the School of Life Sciences. “Open Philanthropy was the only organization that responded to support our high-risk project, the biggest cancer intervention trial in dogs ever. I really admire them for that.”

Searching for a vaccine

It is widely thought that all cancers are unique and therefore a general, preventative vaccine would not be possible. However, Johnston’s team has discovered a potentially high-impact way of identifying tumor antigens that are common among cancers; these make up the key components of their vaccine.

The new vaccine, called a multi-valent frameshift peptide (FSP) vaccine, was developed by Johnston and his team over the last ten years. The vaccine already has been tested for efficacy in mice and is shown to be safe in dogs.

Johnston and his team eventually want to take the next leap and test the vaccine in humans. However, they feel that first testing the vaccine in dogs has many advantages. 

Cancer is the leading cause of death in pet dogs and their cancers are very similar to their human counterparts. Some breeds have a very high cancer rate, as much as 40 percent. The canine immune system responds to tumors and vaccines similarly to that of humans, but the course of tumor development in dogs is much shorter. Johnston thinks they can evaluate the effectiveness of the vaccine in five years or less, versus the 15 to 20 years it would take in a human trial. The vaccine they are testing in dogs will have a comparable composition to the one they would test in people.

“We have been working over 10 years to develop a vaccine that could potentially prevent any cancer,” said Luhui Shen, senior science director of the vaccine project. “Our next goal is to test the vaccine in owner-enrolled, healthy dogs. We are fairly confident that if the vaccine works in dogs, it could work in people.”

How the trial will work

The trial will be conducted under the direction of Douglas Thamm, director of clinical research at the Flint Animal Cancer Center at Colorado State University. Healthy, middle-aged pet dogs will be enrolled, continuing to live their normal lives at home and receiving biannual exams with a complete clinical pathology workup. 

Dogs will be randomly chosen to receive either the vaccine or a mock version. Dogs receiving the mock vaccine are expected to develop cancer at normal rates. The experiment will determine whether the test vaccine can prevent cancers.

Any owner whose dog develops cancer during the trial, on either the test or control arm, will be given a credit toward medical expenses.

If successful, this trial would provide strong support for the concept of employing FSP vaccines to prevent cancer in its earliest stages, possibly leading to a canine cancer vaccine, and could eventually justify human clinical trials for both treatment and prevention.

“We consider this a high-risk project with an unusual opportunity for high impact as it could possibly reduce the incidence of cancer and cancer metastasis,” the Open Philanthropy Project grant announcement said. “We believe cancer preventative vaccines have a higher expected value than curative cancer therapies, since an effective vaccine would likely be a less expensive way to provide decades of healthy life compared to current cancer therapies, which often only extend life for a few months or years. We also believe cancer vaccines would be tractable in developing countries, which have a high cancer burden. FSP vaccines are particularly attractive compared to other proposed cancer vaccines because they may work against many cancer cell types.”

A daring gift

Cancer is increasingly placing a toll on developing countries, according to a World Health Organization (WHO) report published in 2010. The latest WHO statistics cite that cancer causes around 7.9 million deaths worldwide each year. Of these deaths, around 70 percent, or 5.5 million deaths, are now occurring in the developing world. A disease once associated with affluence now places its heaviest burden on the poor and disadvantaged who can not afford the advanced treatments available in developed countries, some of which cost $200,000 or more. 

“If the vaccine works it should be inexpensive enough that everyone in the world could get it,” according to Johnston.

Johnston foresees this commitment on the Open Philanthropy Project’s part to be an inspiration to other philanthropic efforts to be more daring and risk-taking.

“It wasn’t easy to identify an organization interested in funding such a trial,” Johnston said. “Open Philanthropy came to us, rigorously reviewed our proposal and offered to fund the trial. We are extremely grateful that they would support this high-risk effort.  This vaccine may not work, but if it does it will be thanks to the commitment of Open Philanthropy to funding potentially transformative efforts.”

Johnston is the director of the Biodesign Center for Innovations in Medicine and CEO of Calviri, Inc, a cancer vaccine company. He is known for his success as an innovator, inventor and disruptor of conventional science.

Johnston and his interdisciplinary team have developed a system for continuous, comprehensive, inexpensive health monitoring known as immunosignature diagnostics. More recently, his team successfully answered a call from the U.S. Department of Defense via the Defense Advanced Research Program Agency, or DARPA, to develop a technique for producing 1,000 doses of an antimicrobial in a week — a discovery that will potentially safeguard populations that are threatened by infections and outbreaks of Ebola and Zika.  

Top photo courtesy of Pixabay.com.