CBS “Sunday Morning” this weekend will take viewers into the Fred Hutchinson Cancer Research Center lab of Dr. Jim Olson to show how Tumor Paint, a “molecular flashlight” he discovered that’s derived from scorpion venom, distinguishes cancer from healthy tissue. The show will air in the Seattle area from 7 to 8:30 a.m. Sunday on KIRO-TV.
During his interview with CBS correspondent Susan Spencer, Olson said that if Tumor Paint is approved by the U.S. Food and Drug Administration, “I think this will potentially be the biggest improvement in cancer surgery, maybe, in 50 years.”
The award-winning newsmagazine, a Sunday morning staple for many, first aired in 1979 and is hosted by journalist Jane Pauley. The program reaches about 6 million viewers across the nation each week.
Fred Hutch has licensed the technologies relating to Tumor Paint to Blaze Bioscience and has an ownership interest in Blaze. Olson has an ownership interest in Blaze Bioscience. Both Fred Hutch and Olson may financially benefit from their interests if the company is successful in marketing this product. The terms of the financial arrangements with Blaze Bioscience have been reviewed and approved by Fred Hutch in accordance with its conflict of interest policies.
Tumor Paint is an investigational product and has not been approved for commercial marketing by the U.S. Food and Drug Administration or any other regulatory authority. No conclusions should be drawn from the information in this story about the safety, efficacy, or likelihood of regulatory approval of this investigational product.
— Kristen Woodward / Fred Hutch News Service
Three groups of researchers at Fred Hutchinson Cancer Research Center have received a total of $800,000 in grants to investigate approaches to overcoming the main barrier to an HIV cure: reducing reservoirs of virus that lie dormant in some of the longest-lived cells of the body.
All of the grants — announced on the same day last month — are from the New York-based American Foundation for AIDS Research, or amfAR, as part of its Countdown to a Cure initiative. Two of the grants, to Drs. Keith Jerome and Hans-Peter Kiem, respectively, will fund research in preclinical models on cell and gene therapies.
A two-pronged approach to reaching T cells
Jerome received a $400,000 grant to develop a way to make sure that cell and gene therapies get to the right cells in the body: the type of T cell (a part of the immune system) that HIV targets.
“Anything you do with HIV, you have to get to T cells,” he said. “But it turns out that T cells are hard to get into. An even bigger problem is that they are spread throughout the body. So how do we take these cell and gene therapies that we’re developing and have a mechanism to get them to the T cells?”
Working with co-investigators Dr. Dan Stone of the Hutch and University of Washington microbiologist Dr. Shiu-Lok Hu, Jerome will modify an adeno-associated virus to act as a viral vector — a virus that delivers a therapy by infecting a cell but does not itself cause disease. To make sure it reaches the right cells, the team will destroy its usual way of getting into cells and then add an engineered protein called a designed ankyrn repeat protein, or DARPin, that only allows the virus to infect T cells.
Additionally, Jerome’s team will inject the DARPin-modified adeno-associated virus subcutaneously rather than intravenously so that it will travel via the lymphatic system to the lymph nodes, where T cells reside.
“The grant is to optimize the delivery system,” Jerome said. “If we’re successful, in a later phase we’ll partner with other amfAR grantees who are working on the payload.”
Jerome and collaborators also are working under an earlier amfAR grant to develop nanocarrier technology to deliver therapies to reservoirs of dormant, HIV-infected cells.
Modifying stem cells to deliver broadly neutralizing antibodies
Kiem, working with Dr. Anne-Sophie Kuhlmann in his laboratory, received $200,000 to genetically modify blood stem cells to deliver anti-HIV therapies — specifically, in this case, broadly neutralizing antibodies that have been shown to target HIV. (Other scientists, including those at the Hutch, also are testing such antibodies as a way to prevent HIV.) Kiem’s strategy seeks to address a challenge in deploying broadly neutralizing antibodies against HIV: how to get them to persist in the body long enough to do the job.
Because stem cells give rise to all the blood cells in the body — and because such cells are continually replaced as they die off— modifying stem cells and thus stem-cell derived blood cells to produce broadly neutralizing antibodies would lead to a steadily replenished supply of the antibodies.
It would also ensure that the broadly neutralizing antibodies get to the right places because all blood cells travel to relevant HIV reservoir sites, including the brain and central nervous system, lymph nodes, liver, lungs and spleen, Kiem said.
Under a separate grant, Kiem’s lab is working on using gene editing to create HIV-resistant stem cells.
Scientists consider cell and gene therapies to be a promising approach because the only person known to be cured of HIV — Timothy Ray Brown — was cured following a stem cell transplant to treat acute myeloid leukemia. Brown’s doctor found a matching stem cell donor who carried two copies of a rare HIV-protective genetic mutation. Because transplants are associated with substantial side effects for anyone not also facing a life-threatening cancer, scientists are working to develop less toxic, more widely applicable cell and gene therapies.
Kiem, a stem cell transplant and gene therapy researcher, and Jerome, an expert in viral diseases, are co-directors of the Fred Hutch-based research group defeatHIV, one of the first groups to receive funding for HIV cure research from the National Institute of Allergy and Infectious Diseases — in 2011 and again in 2016.
‘It’s a very simple idea’
Separate from the cell and gene therapy competition, Schiffer and Hladik received a $200,000 amfAR grant to test whether an anti-proliferative agent called MMF (mycophenolate mofetil) — an already licensed drug used to treat rheumatologic diseases, prevent rejection after solid organ transplants and prevent graft-vs.-host disease after stem cell transplants — can reduce the size of the HIV reservoirs. MMF works by limiting T-cell proliferation, and Schiffer and Hladik hypothesize that slowing the replication rate of latently infected T cells would shrink and may even eventually eliminate the reservoir.
In a paper published online in the journal Scientific Reports, Schiffer and Hladik called the strategy a “compound interest cure,” alluding to the small changes over time that lead to big savings.
“It’s a very simple idea compared to the other technologies being proposed for HIV cure,” said Schiffer, a physician and mathematical modeler.
When HIV targets a T cell, it inserts itself directly into the host cell’s genome and hijacks the cell’s machinery to make copies of itself that go on to infect other T cells. Combination antiretroviral therapy, which came into use in 1996, holds HIV in check by preventing the virus from multiplying, lowering the amount of HIV in the blood (called the viral load) to near undetectable levels.
After the drugs were first introduced, it was thought that they might actually cure infection. But the drugs can’t reach the latent HIV reservoirs, where HIV essentially hibernates within human chromosomes without replicating. Given the rate at which latent HIV “wakes up” naturally, scientists have come up with a depressing estimate of how it long it would take for antiretroviral therapy to eventually eliminate HIV: around 70 years.
But MMF would keep the T cells themselves from replicating, and Schiffer and Hladik hypothesize that it is cell proliferation that sustains the reservoir. The mathematical model developed by Schiffer and Drs. Dan Reeves, a physicist in his lab, and Elizabeth Duke, an infectious disease physician who cares for people with HIV, shows that HIV-infected patients on antiretroviral treatment who also take an anti-proliferative drug such as MMF could clear the reservoir within two to 10 years.
The clinical trial, which will enroll five participants with HIV and run for two years, is slated to begin in September at the Harborview Medical Center HIV Clinic (Madison Clinic).
MMF does have potential side effects. It can cause nausea. And because it is an immune-suppressive agent for preventing organ rejection, people who receive it need to be watched closely to avoid infections. (Schiffer and Hladik also are working with Jerome on the nanocarrier technology to better target MMF delivery so that not all T cells are affected.)
For now, what particularly excites Schiffer about MMF is that it is an already-licensed drug that is off patent — that is, affordable. If it is found to be effective, it could be rolled out rapidly, even in the low-income countries that are hardest hit by the HIV pandemic.
“In the worst-case scenario, we’ll really learn some fundamental things,” he said. “In the best-case scenario, we’ll hit a home run and be on to something.”
— By Mary Engel / Fred Hutch News Service
The telephone call from Marrakesh, Morocco, was garbled and full of static, and it sounded like it was coming out of a tunnel. Nevertheless, Sandy Ormbrek could tell it was her boss, Dr. Charles Kooperberg, on the other end of the line.
It took some time to understand exactly what he was saying, but the news was as unexpected as it was delightful: She had just won this year’s T. Evans Wyckoff Esprit de Corps Award from Fred Hutchinson Cancer Research Center.
Wyckoff was a founding member of the Hutch’s board of trustees, and the award in his name is meant to recognize in employees the traits he exemplified, including “dedication, enthusiasm, the ability to get things done, and a commitment to the center and its mission.”
Kooperberg, who was attending a World Statistics Congress in Marrakesh, heads the Biostatistics Program at Fred Hutch. For nearly two decades, Ormbrek has been in charge of the administrative team that helps Biostatistics faculty, postdoctoral researchers and staff get their enormously complex work done.
“Undoubtedly, Sandy is the heart of the Biostatistics Program,” Kooperberg wrote in a letter in support of her nomination. “As program administrator, she creates an environment where people can be productive and happy.”
Ormbrek’s support for the scientists includes mentoring junior faculty, students and postdocs, developing and promoting young staff, and “providing sound, thoughtful advice to senior faculty on grants, administrative and career issues,” Kooperberg wrote. “She does this all with high standards, integrity and humor.”
At the Annual Employee Celebration July 19, a campuswide summer barbeque at Fred Hutch, Ormbrek’s award was announced by Dr. Garnet Anderson, senior vice president and director of the Public Health Sciences division, of which the Biostatistics Program is a part. “Sandy manages a stellar team,” she said, “that has lovingly given her the title of Field Marshal to signify her role when she asks them, yet again, to perform heroics.”
Fred Hutch President and Director Dr. Gary Gilliland added, “We’re delighted and very proud of the work you’ve done over the last 32 years.”
Ormbrek joined Fred Hutch in 1985, working in Biostatistics after a five-year stint as a researcher for the Seattle Chamber of Commerce. “It was always important to me to work for a nonprofit,” she said. Over the years, she held a variety of positions at the Hutch and was involved in multiple projects, including the Hanford Thyroid Disease Study, which examined the health effects of radiation exposure in the regions surrounding the Hanford nuclear site. In 2000, she returned to Biostatistics to take on her current role as program administrator. “It felt like I was coming home,” she said.
There are few programs at Fred Hutch that touch so many researchers throughout the organization as Biostatistics, because virtually every major project requires the expertise of biostatisticians in both study design and analysis of findings. Since taking on her current post, the number of faculty in the Biostatistics Program supported by her team has risen from four to 14. That growth reflects both the expansion of the Hutch itself, as well as the massive increase in data generated in today’s research.
Over the course of more than three decades at Fred Hutch, Ormbrek has developed a deep understanding and appreciation for the work that goes on within its walls. “I like change,” she said. “It’s important in my mind that we all evolve our thinking, and always remain flexible and agile.” In fact, there is sign posted on the wall above her desk. In large block letters, it sort of sighs: “OH, EVOLVE.”
As a longstanding employee of Fred Hutch Ormbrek has witnessed plenty of changes, but there is still one constant: “The point of my job,” she said, “is to do whatever we can to facilitate the research, to relieve faculty of any administrative burden so they can focus on the science.”
— Sabin Russell / Fred Hutch News Service