June 27, 2017
By Mark Terry, BioSpace.com Breaking News Staff
At the recent annual meeting of the Association of Genetic Technologists held in St. Louis, Missouri, I had the opportunity to hear a talk by Joshua Schiffman. Schiffman is an associate professor of Pediatrics at the University of Utah, and Medical Director of the High Risk Pediatric Cancer Clinic at Huntsman Cancer Institute. He is also involved in several startup companies, which I’ll get to.
Schiffman, in a way, is pretty famous, even though most people probably haven’t heard of him. But they may have heard about some of his work.
Li-Fraumeni Syndrome
It all started when Schiffman was working with cancer patients that only have a single copy of p53, which is a very well-known tumor suppressor protein. As Schiffman pointed out in his talk, people generally have two normal copies of p53, which gives us about a 50 percent chance of getting cancer. (As opposed to mortality rate from cancer, which in humans is from about 11 to 25 percent). Individuals who only have a single copy have a 100 percent chance of getting cancer, or very close to it. The people with this single copy have Li-Fraumeni syndrome, which is a rare, autosomal dominant, hereditary disorder.
Before I continue, I want to step back just a moment to make a couple general statements about cancer.
• Cancer, which is not a single disease, is loosely defined as uncontrolled, abnormal cell growth.
• The longer an animal lives—even if that animal is a human being—the higher the likelihood of cancer. This makes sense because the longer you live, the more divisions your cells have undergone, and the more likely there is to eventually be an unrepaired mutation that leads to cancer.
• Even more generally speaking, if an animal has a lot of cells, the odds are higher for cancer.
Elephants
Which is where elephants come in. They have about 100 times more cells than humans—in other words, they’re big—and their typical life span is 50 to 70 years. Yet elephants have a mortality rate from cancer of about 5 percent, compared to 11 to 25 percent for people.
According to Schiffman, he had heard this information about elephants, but didn’t give it much additional thought until his wife asked him to take their kids to the Hogle Zoo. While watching the elephant show, he remembered, and asked the elephant trainer if he could ask a question.
“Sure, I’ve heard them all,” the elephant manager, Eric Peterson, said.
“I’m an oncologist. Could I get an elephant blood sample?”
“Except that question,” Peterson replied.
Not only did Schiffman get blood from the zoo’s elephants, but he was later able to get blood samples from the elephants in the Ringling Brothers Circus.
And what did he find?
Elephant genes have 40 alleles of TP53, the gene that produces p53.
And as a bit of an aside, studies have found that 38 of the 40 TP53 genes are retrogenes. This indicates that, from an evolutionary standpoint, these extra genes were selected over a long period of elephant evolution to fend off cancer. There were originally two TP53 genes, but additional genes were added later over time.
The original article in The Journal of the American Medical Association in November 2015.
Nanotechnology
In 2015, Schiffman was at a pediatric oncology conference in Haifa, Israel. He was giving a talk on elephants, p53 and cancer. Avi Schroeder, an assistant professor of chemical engineering at the Technion-Israel Institute of Technology, was in the audience. Schroeder’s research focuses on novel drug delivery using nanotechnology.
The two men met up—in fact, they both had written notes to each other that they should talk.
The theory was that by using Schroeder’s nanotechnology drug delivery systems and Schiffman’s synthetic elephant p53, known as eP53, they might be able to create an anti-cancer delivery system.
So they then founded a biotech startup, PEEL Therapeutics. “Peel” is the phonetic spelling of the Hebrew word for elephant.
eP53 has been successfully encapsulated in nanoparticles, and in petri dishes, has demonstrated proof of concept. In fact, Schiffman showed several quite dramatic videos of their treatment in action, with cancer cells being killed within 24 hours.
PEEL Therapeutics
PEEL Therapeutics is currently in “stealth mode,” so not much is really known about it. Schiffman, like most people reading this column, understands that there is a very long road—often filled with potholes, steep hills, and often land mines—from having something work in the test tube to an approved therapeutic.
The elephant part of the story makes it particularly appealing (no pun intended).
What is particularly intriguing, at least for me, is that if viable—and since I write weekly about promising drugs that crash and burn in late-stage clinical trials, I recognize it’s a big “if”—PEEL’s candidate has the potential to be effective in many different types of cancers.
Schiffman and PEEL and everyone else involved wants to make it very clear that they are not experimenting on elephants. Furthermore, it should be emphasized that the p53 they are using is synthesized, so it no longer relies on elephant blood.
PEEL will presumably begin preclinical trials on animals with cancer. In an article for Brown Medicine Magazine, Schroeder noted that if the therapeutic, which would essentially be a type of gene therapy, is successful in animals, they would consider releasing it for veterinary use. “We have great interest from people who have dogs and pets at home with cancer,” Schroeder said.
Meanwhile, PEEL Therapeutics has the advantage of an intriguing concept, fascinating history, and much-loved mascot.
Mark Terry, a regular writer for BioSpace, is a full-time freelance writer, editor, novelist and ghostwriter specializing in biopharma, clinical diagnostics, medical practice management and resume writing. He has written 1000+ articles and more than 20 books, including the award-winning THE FALLEN. When not writing, he can be found practicing Sanchin-Ryu karate, riding his bicycle or reading.
