Articles & News 

Tuesday
Jun122018

Dorothy Foundation supports the work of Dr. Stephen Johnston

A Shot against Cancer Slated for Testing in Massive Dog Study

 

The canine clinical trial will vaccinate 800 healthy pets

Stephen Johnston dreams of a future in which humans could protect themselves against all types of cancer with a single shot. As the biochemist envisions it, this prophylactic injection would train the immune system to pick off cancerous cells before they could mobilize into malignancies. The catch: many oncology specialists insist this is scientifically impossible.

Critics of the concept say tumor cells are too genetically complex to be consistently thwarted by zeroing in on any one target. Yet Johnston and colleagues at Arizona State University have been working on an experimental inoculation for the past 12 years. They tested blood from hundreds of humans and dogs with cancer to identify potential vaccine targets, then came up with vaccine cocktails and experimentally tested them in hundreds of mice with tumors. The researchers believe they have now identified a recipe that has the right stuff to keep tumors from forming. Johnston says his vaccine cocktail instructions remain unpublished because he made a strategic decision not to release them before securing intellectual property rights.

But this July three U.S. universities will start the next stage of work—testing his candidate vaccine’s ability to prevent all types of cancer in dogs. It will be the largest interventional canine clinical trial ever conducted, involving at least 800 healthy pets. (The second-largest was a cardiology trial with 360 dogs.) Half the dogs will be randomly selected to receive the shot, and the others will be injected with a placebo. Both groups will then be tracked over five years for signs of cancer or any concerning side effects.

Cancer is the leading cause of death in pet dogs, so if this vaccine is successful it would be a boon for their owners. It could also be a game-changer for human cancer research. “It’s exciting he’s doing this in dogs—because dogs are immunologically and genetically similar to people,” says Sasha Stanton, an assistant professor at the University of Washington’s Cancer Vaccine Institute who is unaffiliated with Johnston’s work. Like humans, Stanton says, Labradors, Chihuahuas, huskies and their ilk have a lot of genetic variability and have honed their immune systems in nonsterile environments, which makes them a better test model than lab rodents. Our four-legged friends also get cancer at roughly the same rate as humans do, with a lifetime risk of about 30 to 40 percent. Most of the 100-plus types of cancer identified in people are also found in dogs. In many cancers canine and human tumors are indistinguishable under a microscope. And because dog life spans are shorter and their tumor development is accelerated, Johnston says he can determine a cancer vaccine’s effectiveness in dogs much faster than he could in humans.

Research into cancer vaccines has recently surged, sparked by the growth of immunotherapies that harness the immune system’s power to attack tumors. Since 2014 more than 300 clinical trials of cancer vaccines have taken place worldwide. But most of that work has been on therapeutic inoculations—those tailored to combat a specific patient’s tumor. In using that approach, researchers typically sequence the tumor’s DNA and create a customized treatment cocktail of cancer cell proteins and white blood cells. If all goes well, once that concoction is injected back into the patient its tumor-specific proteins should elicit a strong response from T cells, which help the body destroy the cancer.

By contrast, Johnston says his team at A.S.U.’s Biodesign Institute Center for Innovations in Medicine is trying to develop a universal, preventive cancer vaccine—an injection that could be employed before tumors develop. He may be cornering the market on this preventative effort, because the consensus in the medical community is this: “It’s biologically impossible,” as Maurie Markman, an oncologist and president of medicine and science at Cancer Treatment Centers of America, puts it. “It’s fantasyland. It goes against everything we know today about what cancer is.”

Cancer is considered not one disease but thousands of different maladies, Markman notes. Each individual tumor is fueled by distinct, complicated DNA mutations, he adds, so creating one vaccine to prevent different conditions is widely regarded as impossible. But Johnston says that when his team looked at RNA—the messenger molecules that carry genetic instructions for DNA—common copying errors appeared across all the cancers he tested: five major types in humans and eight in dogs. Johnston says these commonalities led him to believe that cancer might be viewed, for vaccine-designing purposes, as one entity.

The key to Johnston’s approach is focusing on cancer cells’ error rates when they replicate in the body. In order for a cell to build a new version of itself, DNA is first transcribed, or copied, into RNA. The cell reads the RNA and uses that information to produce the appropriate proteins for building a new version of itself. Biologists and physicians know healthy cells are quite competent copiers. But cancer cells, which divide rapidly, make more mistakes in transcription. “In cancer the whole error rate goes up about 10-fold,” Johnston says. He is focusing on one kind of error called a “frameshift,” which is common in cancer cells and strongly stimulates the immune system. In a frameshift an added or deleted molecular building block called a nucleotide throws a wrench into a cell’s replication gearbox. Normally a three-part string of nucleotides (usually represented by letters) codes for a particular type of protein. But an errant or missing nucleotide can gunk up the instructions—leading to gibberish recipes that cannot become a desired protein, but rather a protein component called a peptide. If these peptides have enough irregularities, the immune system may identify them as problems and mark them for destruction. Johnston hopes his vaccine will boost this process by priming two types of immune system workers—memory cells called B cells as well as T cell “soldiers”—to remember and hunt down these peptides.

To design the experimental vaccine, Johnston’s team pored over tumor cells in hundreds of humans and dogs. Out of 100,000 possible frameshifted peptides, they selected 30 that commonly manifest in a variety of cancers in both species. They put those peptides into a vaccine that can be injected into the skin. The idea is that specific cells will grab the peptides and present them to T cells and B cells—akin to showing “Wanted” posters to the immune system’s control officers. This gives T cells a “memory” of the frameshifts—and when the T cells see them, they’ll kill the cells harboring them. Crucially, this early introduction would allow the immune system to destroy such frameshift-bearing cells when they are few, rather than after they have formed a tumor with billions of highly evolved cells.

The process may have risks. For example, noncancerous cells can sometimes produce frameshifts but, Stanton says, such cells tend to be abnormal and would be destroyed anyway. Still, she notes anytime the immune system is stimulated it can attack healthy cells along with mutated ones, bringing a risk of side effects. Johnston says his team previously tested the vaccine in three dogs and detected no safety issues. The clinical trial will look for potential side effects in addition to trying to determine if this vaccine can prevent cancer.

Three sites—Colorado State University, the University of Wisconsin–Madison and the University of California, Davis—plan to inoculate 800 middle-aged dogs for Johnston’s new study. For several years afterward each dog will each receive a booster dose and a physical exam. Johnston thinks the investigators will have some idea whether the prophylactic is working in a year or two. They hope it will protect against as many as 80 percent of new tumors, based on his preliminary tests in human and dog blood leading up to this trial.

Stanton is intrigued by Johnston’s work, but says, “One stumbling block may be that these [frameshifted peptides] may be more or less represented in different tumor types—so you may have one tumor type that this would be particularly effective in whereas in another it would be less so.” Johnston is also considering creating preventive vaccines targeted to specific cancers—such as breast, lung and stomach—based on each one’s characteristic frameshift errors. Stanton says this approach holds greater promise.

Yet Markman remains unconvinced that either approach could work. “I do not in any way wish to criticize this individual or anybody else who’s got an idea and wants to try it and is going to do it in a rigorous manner—I applaud it,” he says. “All I’m saying is the concept is fatally flawed.”

Cancer kills some 8.8 million people yearly, 70 percent of them in low- and middle-income countries where many people cannot afford treatments that cost tens of thousands of dollars, Johnston notes. This is one reason he believes developing a preventative vaccine—and keeping it affordable—is so vital. “No one else has proposed any other way you could possibly make a prophylactic vaccine,” he says. “So if we’re the only game in town, and there’s even a 10 percent chance it might work, we should try it.”

Monday
Nov272017

Dorothy Foundation donates to Biodesign Institute project to diagnose pancreatic cancer earlier  

November 21, 2017

Last year, pancreatic cancer overtook breast cancer as the third leading cause of cancer deaths. With a five-year survival rate of just 8 percent, it is one of the deadliest forms of cancer.

But with early detection, that survival rate rises to 60 percent, even with conventional treatments. That’s why the Dorothy Foundation donated $25,000 to a project led by Stephen Johnston, director of the Biodesign Center for Innovations in Medicine and professor at the School of Life Sciences at Arizona State University.Dorothy Foundation check presentationThe Dorothy Foundation donated $25,000 to the Biodesign Institute at Arizona State University for a project to diagnose Stage 1 pancreatic cancer.Download Full Image

Johnston is hoping to transform the diagnosis of pancreatic cancer. His research aims to detect Stage 1 pancreatic cancer with an immunosignature technology he developed at the Biodesign Institute at ASU.

Johnston said the donation will help him gather blood samples of Stage 1 pancreatic cancer, which are difficult to collect because pancreatic cancer does not create symptoms at early stages. He needs those samples for a pilot study to prove the immunosignature technology works, a key step to developing a reliable and inexpensive diagnostic test.

“We try to push the edge, and we feel this is our responsibility for the university,” Johnston said. “We should be taking the really high-risk chances out there, which often starts just like this. It starts with a little seed fund that’s willing to take a bet, and then we see that catalyze enough interest that we can get the bigger funding to come in, and that’s been our modus operandi for years and years.”

Longtime FOX 10 Phoenix sports anchor Jude LaCava and his sister Sandra LaCava started the Dorothy Foundation to honor their mother, who died of breast cancer at age 49, and accelerate cancer research. Sandra LaCava serves as executive director of the foundation.

“We know the devastation of loss and the tremendous torment that many patients go through, especially when it’s late-stage cancer,” said Jude LaCava. “We’re here to get in the trenches and support the researchers like Dr. Johnston here at ASU Biodesign.”

The Dorothy Foundation presented a check during a ceremony at the Biodesign Institute on Friday morning. Friends of Jude and Sandy LaCava who had lost loved ones to pancreatic cancer joined them at the event, and Johnston gave them a tour of his laboratory and an update on his work to develop better diagnostic tools for cancer.

“I can’t express enough my appreciation for Jude, Sandy and the Dorothy Foundation for giving us continued support for what we’re trying to do here,” Johnston said.

So far, the Dorothy Foundation has donated more than $100,000 to support cancer research at the Biodesign Institute. Eric Spicer, senior director of development at the ASU Foundation, thanked the Dorothy Foundation and the LaCavas personally for their support, which contributes to Campaign ASU 2020.

“Cancer is such an awful thing, and the fact that you all have taken the initiative to establish a foundation in honor of your mom and recognize her legacy in this way is an inspiration to others to also join the fight, so we thank you for that,” Spicer said.

“You’ve chosen Biodesign. You’ve been an advocate for us for a number of years now, and that means the world to us. It’s more than just the dollar figure. That provides us inspiration to keep going, and we’re just incredibly grateful for the support.”

Tuesday
Jan172017

GREAT NEWS FROM THE DOROTHY FOUNDATION AND OUR PARTNERSHIP WITH CANCER COMMONS.

January 2017 -  cancercommons.org

 

The Dorothy Foundation continues to partner with the innovative work at Cancer Commons with the goal of providing more treatment options for current cancer patients. Marty Tenenbaum and Dr. Emma Shtivelman have utilized one of the most innovative information based patient oriented programs to assist patients and their oncologists in the fight against cancer. We urge everyone battling cancer to get the word out on the data sharing that is changing the way we treat cancer through the remarkable work at Cancer Commons. The following letter is one of the most recent success stories. Mary Beth Zolik Smith was one of the most popular radio and news personalities in Ohio (I worked with her during the 1980's). She has quite a story to tell in her fight against Non Hodgkins Lymphoma.  We urge all of you to donate, support and get behind the great work at Cancer Commons just one of the very important partners to the Dorothy Foundation. Please take a minute and review the following letter. 

 

I can not thank you enough for your assist via the Dorothy Foundation in linking me with Cancer Commons. When I reached out to Cancer Commons I was introduced to Emma Shtivelman, Ph D. Emma was one of the most positive, knowledgeable and encouraging persons I have encountered in my long journey to combat NHL. My cancer treatments covered the usual and customary standard of care from chemotherapy to stem cell transfer. None of these interventions worked. My pursuit of information and direction relative to immune therapy and clinical trials  led me to you and your referral to Cancer Commons and Dr. Emma. You were truly the life line I had hoped for. Dr Emma helped me identify several clinical trials that were recruiting clients with refractory NHL. With Emma's resourcefulness I was linked with hospitals in Boston, Tampa, Detroit and Cleveland. I was accepted into the KITE Clinical trial at the Cleveland Clinic in late November of 2016. I had my re-engineered Tcells infused into my system on December 27, 2016 and learned on January 23, 2017 after my most recent PET scan that I had a complete response to the immune therapy. Needless to say,  my family and I are ecstatic with this news and I thank you from the bottom of my heart for your assist in this miracle. Your referral to Cancer Commons was a blessing for which I will always be grateful. If I can in any way help you help others as they navigate their cancer treatment options, please don't hesitate to call me.

Sincerely and with tremendous appreciation,

Mary Beth Zolik-Smith

Sunday
Jan102016

Super Patient: Diane Milne Gives Other Cancer Patients the Tools that Helped Her Survive

June 14, 2014 started out like any other day for Diane Milne. But then, just before the two-hour Zumba exercise class she took almost every morning, she suddenly couldn’t breathe. “I had an overwhelming sense of doom,” recalls Diane, a 68-year-old retired nurse. “I was home alone and I thought I was going to die.”

READ THE FULL ARTICLE HERE

Wednesday
Jul012015

The Dorothy Foundation Launches a Guided Imagery Library for Cancer Patients at Chandler Regional Medical Center 

Guided imagery is a holistic, mind-body therapy that consists of healing words and images, set to soothing music, to achieve specific healing goals. Guided imagery is designed to connect with a person’s innate cancer fighting immune system, which is a person’s strongest ally and oldest friend.

Read the full article here