Dr. Aude Chapuis named Damon Runyon Clinical Investigator; Dr. Jonathan Bricker receives $3.1M NCI grant to test quit-smoking smartphone app; Dr. Hans-Peter Kiem appointed chair of NIH Recombinant DNA Advisory Committee; Dr. Julie Overbaugh receives award from Association for Women in Science
Fred Hutchinson Cancer Research Center immunotherapy researcher Dr. Aude Chapuis received a Clinical Investigator Award this month from the Damon Runyon Cancer Research Foundation. The award will provide Chapuis with three years of support, plus assistance with research costs, to conduct a trial of adoptive T-cell therapy for unresectable non-small-cell lung cancer, or NSCLC, and an asbestos-related cancer called mesothelioma that affects the lining of the lungs.
“It’s a great honor,” Chapuis said. “The information that we’ll be able to extract from this trial is going to help us significantly ameliorate future adoptive immunotherapy.”
Chapuis’ Damon Runyon–supported trial will extend the use of an immunotherapy target called WT1 to NSCLC and mesothelioma. T cells engineered to attack WT1-bearing leukemic cells were developed in the laboratory of Fred Hutch’s Dr. Phil Greenberg. A similar clinical trial in patients with acute myeloid leukemia, using the same T-cell receptor, is currently underway.
Like many leukemia cells, many NSCLC and mesothelioma cells overproduce WT1, making them equally vulnerable to recognition and attack by T cells that identify the target. “This target is overproduced in NSCLC and is one of the signatures of this cancer,” said Chapuis, who is an assistant member of Fred Hutch’s Clinical Research Division and an assistant professor at the University of Washington School of Medicine.
The trial is a collaborative effort; As co-principal investigator, Chapuis oversees the laboratory work and is responsible for generating T-cell products and analyzing the outcomes. Dr. Sylvia Lee is the trial's co-principal investigator, responsible for the clinical work. The trial is designed to perform a head-to-head comparison of two types of T cells engineered to express a WT1-specific TCR: naïve T cells and central-memory T cells.
“The twist to this research is [that] there’s a lingering question about which substrate cells we should use to plug our T-cell receptors in,” Chapuis said. The trial will provide evidence as to which type of engineered T cell provides better outcomes for patients, she said, and inform the design of future trials.
The trial’s other aim is to test whether a modified version of the WT1 T-cell receptor can not only engage CD8+ T cells (also known as killer, or cytotoxic T cells) but also CD4+ T cells (sometimes called T helper cells) in the immune system's response against WT1-positive cancer cells.
The Damon Runyon Clinical Investigator Award “supports independent young physician-scientists conducting disease-oriented research that demonstrates a high level of innovation and creativity,” according to the cancer research foundation. In addition to providing awardees with research support, the foundation also retires up to $100,000 of outstanding medical school debt. The goal of the award is to increase the number of physician-scientists engaged in bench-to-bedside cancer research.
Five Damon Runyon Clinical Investigators are named each year from around the United States. Previous awardees at Fred Hutch include Dr. Cameron Turtle (2013), Dr. Marie Bleakley (2011) and Dr. Brian Till (2010).
Dr. Jonathan Bricker, a behavioral scientist at Fred Hutch and the University of Washington, has received a $3.1 million, five-year grant from the National Cancer Institute to conduct a randomized, controlled clinical trial of SmartQuit, a smoking-cessation smartphone app.
The new trial follows on the heels of a pilot randomized trial of SmartQuit he conducted in collaboration with UW and 2Morrow Mobile – the first randomized, controlled trial comparing the effectiveness of smoking-cessation programs delivered via mobile apps.
“The funding gives us an amazing opportunity to update our SmartQuit app with state-of-the-art computer science and psychology technologies closely informed by several years of research we have done on prior versions of the app,” Bricker said. Following these key updates, Bricker plans to launch a large-scale, nationwide, randomized controlled study of SmartQuit next year. This new study, which will involve more than 1,600 adult smokers, will compare Bricker’s app with an app that follows the U.S. Clinical Practice Guidelines.
Bricker studies acceptance and commitment therapy, or ACT, to help people quit smoking and other unhealthy behaviors. Unlike traditional quit-smoking approaches, which focus on willpower and avoiding one’s urges to smoke, ACT focuses on increasing one’s willingness to accept the physical, mental and emotional challenges of quitting while also encouraging commitment to engage in values-based behavior change. For more about ACT, see his TEDxRainier talk.
The goal of this new study, Bricker says, is to definitively determine whether an ACT-based app is effective for smoking cessation. Along with collaboration from the Hutchinson Institute for Cancer Outcomes Research (HICOR), the study will also test the cost-effectiveness of the ACT app.
“These are exciting times in the mobile health space,” Bricker said.
“There is a wide chasm between what is available on the market … and what is actually proven to work,” he said. “We feel very fortunate to lead these efforts to impact the science of mobile health and address the critical need for low-cost, high-impact smoking-cessation programming.”
The pilot study that made this larger clinical trial possible was funded by the Hartwell Innovation Fund, a philanthropy initiative established by Dr. Lee Hartwell, Fred Hutch president and director emeritus. The mission of this translational research fund is to support “innovative and high-risk, high-reward activities that may be difficult to fund through government grants or that need immediate support.”
“We took a philanthropy-funded grant of $140,000 and, in less than three years, turned it into a $3.1 million grant. That is more than a 2,200 percent return on investment,” Bricker said. “Now, with this federal funding to continue the work, we have an opportunity to make a huge impact on saving lives and reducing the number of smokers in the world.”
National Institutes of Health Director Dr. Francis Collins has appointed Fred Hutch clinical researcher Dr. Hans-Peter Kiem as chair of its Recombinant DNA Advisory Committee. This federal advisory committee provides recommendations related to basic and clinical gene therapy research. Human gene therapy involves the transfer of recombinant or synthetic nucleic acid molecules into humans to treat certain health problems by compensating for defective genes.
Kiem, associate head of Transplantation Biology at Fred Hutch and a professor of medicine and adjunct professor of pathology at the University of Washington, will begin his term Aug. 1, which will end July 31, 2016. He has served on the Recombinant DNA Advisory Committee, or RAC, for the past four years.
The RAC is a panel of up to 21 national experts from the fields of science, medicine, genetics, ethics and patient perspectives that considers the current state of knowledge and technology regarding human gene-transfer research with recombinant or synthetic nucleic acid molecules.
Human gene transfer may help improve genetic disorders, particularly those caused by inborn errors in a single gene, such as sickle-cell anemia and hemophilia. It also may hold promise for diseases with more complex origins, like cancer and heart disease. Gene transfer is also being studied as a possible treatment for certain infectious diseases, such as AIDS, an area that Kiem and his colleagues are exploring via the defeatHIV consortium.
Dr. Julie Overbaugh, an HIV researcher in Fred Hutch's Human Biology Division, was honored Wednesday night with the 2015 Award for Scientific Advancement from the Seattle chapter of the Association for Women in Science. AWIS hailed Overbaugh for her contributions to HIV research and nurturing the next generation of female scientists.
Overbaugh spoke to a packed audience about her scientific career and philosophy. “Science is social,” she said. “It’s important to choose people to work with because you enjoy working with them. It makes science more productive and fun.”
Her own work has benefited enormously from collaborations with scientists who share common goals and values while remaining inclusive of diverse perspectives, she said. Overbaugh's research has advanced understanding of how HIV is transmitted and the character of the resulting immune response – insights that have informed treatment and vaccine design.
Though she began her career as a basic scientist studying virology, Overbaugh soon transitioned to more translational work at a time when such interdisciplinary projects were rare. She began collaborating with researchers in Kenya studying HIV who needed help with diagnostics and virology. “I was able to go with something that felt like the right kind of work,” Overbaugh recalled of her decision to change the focus of her lab.
With her Kenyan colleagues, Overbaugh helped establish one of the longest-standing, natural HIV-infection cohorts. Using data from this group of research subjects, the team was among the first to show that HIV-infected individuals remain at risk for reinfection, or superinfection. This group also continues to allow Overbaugh to examine the antibody responses, properties of transmitting viruses and viral diversity of HIV-infected patients.
Working with a separate group of mothers and infants, Overbaugh and her collaborators were able to measure the risk of maternal-to-infant HIV transmission through breastfeeding. Most recently, her team was the first to show that HIV infection in infants generates potent, broadly neutralizing antibodies — a rare occurrence in adults.
Overbaugh has mentored more than 60 female scientists in her career, 20 of whom have gone on to leadership positions in academia and industry. Her commitment to fostering scientific creativity through work-life balance continues to inspire her colleagues. One mentee wrote, “Now that I have my own lab, I make an active effort to imitate Julie’s mentoring style, and my personal and professional lives are richer for it.”
Overbaugh encouraged the audience to find fulfillment in all aspects of life, inside and outside the lab. “The demands in science are greater for this generation than for mine,” she observed, but she cautioned her listeners against letting the demands of a scientific career overtake all. “Don’t put off other things in your life. When you learn how to balance, you are acquiring the skills you need to go forward.”