Fred Hutchinson Cancer Research Center's Dr. Colleen Delaney, director of the Cord Blood Program, and Dr. Harlan Robins, head of the Computational Biology Program, were among 18 honorees in Seattle Business magazine’s 2016 Leaders in Health Care Awards. They received the honor at a Feb. 25 award ceremony at the Marriott Waterfront in downtown Seattle.
Delaney, an associate member of the Clinical Research Division and Madeline Dabney Adams Endowed Chair in AML Research, received the Outstanding Medical Research award for pioneering methods to make umbilical cord blood transplants more readily available and successful worldwide. Because it doesn’t need to be as perfectly tissue-matched to the patient as bone marrow, cord blood offers an option to those thousands of blood cancer patients every year who cannot find a matched donor.
She founded the Hutch’s Cord Blood Program in 2006, which has since treated some 300 blood cancer patients from throughout the U.S. and internationally.
“My biggest inspiration and motivation has been and always will be the patients I am privileged to care for,” she told Seattle Business. “They by far have the toughest job, as we all know that cancer sucks and so does the treatment and we are not always successful. It is an amazing feeling to develop therapies that make a palpable difference for cancer patients of all ages and more than enough motivation to push even harder until all my patients are successfully cured.”
Delaney’s cord blood research was commercialized in December 2015 with the launch of Seattle-based Nohla Therapeutics, a stem-cell therapy company focused on off-the-shelf, on-demand universal donor therapies that require no tissue-type matching. She serves as the company’s chief medical officer.
In her effort to broaden the application of cord blood transplantation beyond cancer treatment, Delaney also has received a $10 million contract from the U.S. Department of Health and Human Services Biomedical Advanced Research Development Authority to test expanded cord blood as an “off-the-shelf” product to treat people for acute radiation exposure in the event of a nuclear attack.
Robins, an associate member of the Public Health Sciences and Human Biology divisions at Fred Hutch, received the Outstanding Achievement in Medical Technology award. He is also co-founder and chief scientific officer of Seattle-based Adaptive Biotechnologies Corp., which harnesses the power of computational biology, immunology and molecular biology to analyze millions of molecules — known as receptors — located on the surface of T cells and B cells. This information helps researchers and scientists to better understand at a cellular and molecular level how a patient’s body responds to antigens, with applications in therapeutic monitoring and drug discovery.
Robins’ research at Fred Hutch focuses on the adaptive immune system and its response to viral infection, with HIV a particular area of interest. Taking advantage of new high-throughput sequencing technology, in collaboration with experimental groups, he and his colleagues isolate and sequence the T-cell receptors from millions of T cells in parallel. With this new technology, they can identify and track the complete cellular adaptive immune response to a pathogen, cancerous cells or autoimmune reactions.
Robins is inspired by being able to “translate the science from our research platform to help inform diagnostics and therapeutics that can actually help people,” he told Seattle Business.
— Kristen Woodward / Fred Hutch News Service
A study by researchers at Fred Hutch published in Lancet Haematology found that cytomegalovirus, or CMV, viral load is associated with mortality after blood stem cell transplantation, opening the door to using viral load as a surrogate endpoint for clinical trials testing new, less-toxic treatments for the deadly virus.
That CMV can be lethal for transplant patients is not new. Up until the 1980s, CMV pneumonia was the leading infectious cause of death among transplant recipients, with a fatality rate of 85 to 90 percent.
“Almost everyone died who had CMV pneumonia,” said Dr. Michael Boeckh, the senior author of the new study and a member of the Vaccine and Infectious Disease Division at Fred Hutch.
Although CMV pneumonia is still a deadly complication today, far fewer transplant patients now develop it because they are treated with antiviral drugs, either prophylactically or pre-emptively, using sensitive tests for the earliest signs of infection developed by Boeckh and other Hutch researchers.
But because the current drugs are so good at preventing CMV pneumonia, it’s been difficult for pharmaceutical companies to conduct clinical trials testing new drugs that might have fewer toxic side effects than the drugs in use.
“It’s been hard for companies to prove that their products are any good because the U.S. Food and Drug Administration and other regulatory agencies have required them to show a decrease in CMV disease, but since the standard of care is so good, there have been a lot of [clinical trial] failures, even though the drugs being tested may be effective and have important differences in side effect profiles,” said Dr. Margaret Green, an infectious disease specialist, a researcher in Fred Hutch’s Vaccine and Infectious Disease Division and the study’s lead author.
The need for new, less-toxic treatments was underscored by the study’s second finding — that any CMV viral load is associated with an increased risk of death in the first year after transplant, despite the effectiveness of antiviral pre-emptive therapy in preventing CMV disease. While the higher the load, the greater the risk, even the very low levels that trigger pre-emptive therapy carry some risk.
Pre-emptive therapy has largely replaced prophylactic therapy — given before any virus is detected — because the antiviral drugs in use can cause significant bone marrow suppression or kidney damage, leaving transplant doctors to weigh the risks of CMV disease development against treatment toxicity. The study suggested that prophylactic treatment of CMV may be better than today’s standard of pre-emptive treatment — but only if new treatments that have less toxic side effects are developed.
“New drugs are urgently needed because presently licensed antiviral drugs have important side effects,” wrote Dr. Per Ljungman in an editorial accompanying the study. “Establishment of a surrogate endpoint such as viral load for studies of CMV would therefore be of major importance, such as is the case for HIV and Hepatitis C virus.”
The retrospective cohort study, published online last month, looked at 926 patients who received allogeneic stem cell transplants at Fred Hutch between 2007 and 2013. It was the first to look at different viral load thresholds and also the first to use a new World Health Organization standard measurement, making the data more easily comparable across institutions.
— Mary Engel, Fred Hutch News Service
The Tumor Paint BLZ-100 brightly illuminates head and neck tumors and may also be used to distinguish between high- and low-risk precancerous oral dysplasia, according to new research from Fred Hutch’s Dr. Eddie Méndez and the University of Washington’s Dr. Fred Baik, published Feb. 18 in JAMA Otolaryngology – Head and Neck Surgery. In a preclinical model of head and neck cancer, the team showed for the first time that the fluorescent, tumor-specific optide, developed by Fred Hutch spinoff Blaze Bioscience, highlights head and neck tumors brightly but leaves healthy tissue dim. In a separate model of precancerous early-stage cell overgrowth, the researchers demonstrated that BLZ-100 makes cells at higher risk of progressing to cancer glow more brightly than cells with low risk of becoming malignant.
The study shows that "BLZ-100 can help identify where tumors end and where normal tissue begins,” said lead author Baik, a head and neck cancer researcher and surgeon at UW. “Especially in the head and neck, where sparing normal tissue is crucial for preserving speech, swallowing and facial aesthetics, BLZ-100 could be an important guide for head and neck surgeons.”
In addition to broadening the application of BLZ-100 to fluorescence-guided head and neck tumor surgery, “this study is the first to demonstrate that BLZ-100 can identify high-risk precancerous lesions of the oral cavity,” said Méndez, a head and neck surgeon at UW who also performs research on head and neck tumors in the Clinical Research Division at Fred Hutch.
The team used a preclinical model of implanted, human head and neck cancer cells to show that, after injection, BLZ-100 concentrated in the tumors, particularly accentuating their edges — exactly the region surgeons most need defined in order to ensure that they remove as much tumor as possible without also taking healthy tissue.
Oral dysplasia was triggered in a separate model using a carcinogenic compound painted inside the cheeks. When the researchers injected BLZ-100 and then removed sections of cell overgrowth, they saw that the intensity with which samples glowed correlated with the grade of dysplasia. This suggests that BLZ-100 could be used to help determine which patients with oral dysplasia are at higher risk of progressing to full-blown cancer.
“This would allow clinicians to screen for and treat these lesions before cancer develops,” Méndez said.
Blaze Bioscience provided BLZ-100 as well as funding and housing for the model organisms used in the research.
— Sabrina Richards / Fred Hutch News Service
Dr. Stephen Tapscott, a neurologist and researcher in the Human Biology and Clinical Research divisions at Fred Hutch, has been appointed as a new member of the National Institute of Arthritis and Musculoskeletal and Skin Diseases advisory council. The council comprises scientific and lay members who have expertise in the mission areas of the institute. As a council member, Tapscott will provide advice to the institute on broad policy issues and make recommendations on research priorities.
Tapscott is among four new NIAMS advisory council members announced Feb. 2 at an advisory council meeting at the National Institutes of Health in Bethesda, Maryland.
“I am delighted to welcome these four accomplished individuals to the council,” said NIAMS Director Dr. Stephen Katz. “Each of them brings a critical perspective to the council’s deliberations as we work together to fulfill the institute’s mission.”
Tapscott’s Hutch laboratory studies epigenetics and gene transcription in normal development and disease. His research focuses on gene expression in certain cancers and muscular dystrophies, as well as gene and cell therapies for muscular dystrophy.
— Kristen Woodward / Fred Hutch News Service