Since 2009, the Bezos family has donated and leveraged more than $40 million to Fred Hutchinson Cancer Research Center in support of immunotherapy research, which harnesses the power of the immune system to kill cancer. Thanks to their generosity, the Immunotherapy Integrated Research Center at the Hutch recently held an internal grant competition for immunotherapy projects with high potential to lead to future collaborative research.
The winner: a team of Hutch researchers led by brain cancer researcher Dr. Eric Holland that has received $400,000 for a two-year pilot study to test several novel immunotherapy approaches for glioma, an aggressive brain cancer that affects more than 688,000 people in the U.S. Ultimately, the research will speed the development of new treatments to improve prognosis for these patients, who have a median survival of only 15 months after diagnosis.
“The standard of care for patients with these tumors — surgery followed by radiation and chemotherapy — has not changed in decades, and neither has the outcome. We hope through this work to change the standard of care and prolong survival for glioma patients,” said Holland, who is director of Seattle Translational Tumor Research and senior vice president and director of the Human Biology Division at Fred Hutch.
To develop new therapies before they can be tested in patients, Holland’s lab has developed a genetically engineered mouse model that is representative of human gliomas. Holland and colleagues from the Hutch's Clinical Research Division plan to use these mouse models to test several forms of immunotherapy that target both the tumor cells and other clinically relevant cells surrounding the tumor, known collectively as the tumor microenvironment.
Previous clinical trials testing the ability of the immune system’s T cells to kill glioma tumors have been unsuccessful, Holland said, most likely because brain tumors have few or no T cells to target. However, brain tumors do contain a large number of macrophages — white blood cells that continuously patrol the body, engulfing and consuming foreign substances, defective cells and pathogens. However, cancer cells can evade this search-and-destroy process and turn macrophages into immunosuppressive co-conspirators that promote tumor growth and metastasis.
Dr. Matthias Stephan is leading a project that aims to resolve this problem by using nanoparticles to genetically switch these rogue macrophages back into tumor-killing machines. “Our goal is to develop an off-the-shelf reagent that can quickly reprogram the patient’s [macrophages] to identify and eliminate cancerous cells,” he said. Stephan’s long-term goal is to translate this technology into the clinic as a new approach for treating not only brain cancer but other solid tumors.
Dr. Hans-Peter Kiem is overseeing a project that will evaluate two candidate antigens for CAR (chimeric antigen receptor) T-cell therapies targeting glioblastoma and the tumor microenvironment. One of the antigens identified in his lab, Neuropilin-1, is highly expressed, or upregulated, by both the tumor and immunosuppressive tumor microenvironment. “Gliomas are especially difficult to treat because of their heterogeneous composition and the suppressive microenvironment,” Kiem said. “As a consequence, when targeting a single tumor-associated antigen expressed at the surface of the tumor, other cells from the same tumor that do not express this antigen will escape treatment. The novelty that Neuropilin-1 is expressed both by tumor cells and cells from the microenvironment represents a combinatorial approach with only one target,” said Kiem, who holds the Endowed Chair for Cell and Gene Therapy. Collaborating with Kiem on the project is co-investigator Dr. Anne-Sophie Kuhlmann, a postdoctoral research fellow in his lab.
Dr. McGarry Houghton is leading a project that will investigate the role of the neutrophil, a type of white blood cell that exists in the microenvironment of gliomas and is thought to play a role in promoting tumor growth. His lab is attempting to induce a natural immune response by introducing an antibody that depletes neutrophils in the tumor microenvironment. He hypothesizes that will induce the proliferation of cancer-killing T cells and allow them to infiltrate the glioma. “Ultimately, we plan to show that depleting neutrophils from gliomas will enhance the immune response and the efficacy of immune-based therapies for glioma patients,” he said.
— Kristen Woodward / Fred Hutch News Service
Women who have had breast cancer are at increased risk of developing another primary cancer in the other breast, known as a contralateral breast cancer. Depending on age and the presence of other risk factors, 3 to 20 percent of women with breast cancer will go on to develop a contralateral tumor within ten years of their first diagnosis, but researchers don’t fully understand the risk factors behind those second cancers.
Fred Hutch epidemiologist Dr. Kathleen Malone and colleagues have just received a $7.1 million, 4-year grant from the National Cancer Institute to address this gap. It’s important for women and their doctors to have an accurate estimate of their risk of developing a second primary cancer, Malone said, because women at high risk may benefit from heightened surveillance, prophylactic treatment such as tamoxifen and/or consideration of how their first cancer therapy choice might decrease risk of later cancers. But it’s also important for women at low risk of another cancer to know of their risk, Malone said, pointing to the rising rates of prophylactic mastectomies in the unaffected breasts of breast cancer patients — even among women without a known cancer-driving mutation such as those in the BRCA 1 and 2 genes.
For some with breast cancer, such as those with mutations BRCA1/2 mutations, which have been associated with three- to four-fold increases in risk of contralateral breast cancer, removing the unaffected breast may be medically advised. But the majority of women with breast cancer don’t have BRCA mutations and for them, there is a scarcity of information to guide risk assessment. Whether women are at high or low risk of contralateral breast cancer, knowing their risk status can help inform treatment decisions and help them feel reassured about those decisions, Malone said.
“Women should know where they fall in that risk spectrum,” she said.
The new study spans multiple centers, Malone said, and builds on an existing large population-based study of women with one or two primary breast cancers, known as the Women’s Environmental, Cancer, and Radiation Epidemiology (WECARE) Study. The newly-funded study focuses on identifying molecular biomarkers for risk of a second primary breast cancer and will study the tumors of approximately 1,100 women, half who had only a single primary breast cancer and half who went on to develop a contralateral tumor. Along with Malone, Dr. Jonine Bernstein from Memorial Sloan Kettering Cancer Center is the other Principal Investigator on this project. Fred Hutch researchers involved in the study include Drs. Peggy Porter and Li Hsu. The other participating institutions include the Cancer Prevention Institute of California, the Sinai Health System in Toronto and the University of Iowa.
Additionally, two Fred Hutch translational researchers recently received recognition — and funding — for their work in breast cancer research:
— Rachel Tompa and Diane Mapes / Fred Hutch News Service
The National Cancer Institute has awarded $24 million to Fred Hutch to continue operating the NCI’s primary public access point for cancer information in both English and Spanish.
With the new contract, the Contact Center — previously known as the Cancer Information Service — will emphasize clinical trial education and referrals, increasing outreach to medically underserved populations and integrating innovative communication technologies.
“We are constantly adapting to meet people’s information-seeking needs,” said Nancy Gore, director of the Contact Center, which provides free phone and online help to cancer patients and their families.
The National Cancer Institute originally established contact centers at several NCI-designated cancer centers throughout the country; the first call was taken in 1976. The Contact Center at Fred Hutch joined this effort in 1981, and eventually became the sole operator in 2009, when NCI consolidated existing operations into a single Contact Center.
Gore has worked at the Contact Center at Fred Hutch for 23 years and manages a team of about 65 employees, including cancer information specialists who answer inquiries and oncology-certified nurses who provide technical assistance on interactions and are members of the training team for new staff.
The group handled close to 92,000 inquiries last year. People can reach the service Monday through Friday, 9 a.m. – 9 p.m. ET by calling 1.800.4.CANCER (800.422.6237), through online live chat or by email. Bilingual (English-Spanish) staff members are available on all access channels.
Eric Suni, who has been a cancer information specialist with the Contact Center since 2010, is equipped with a headset, computer and scratchpad for notetaking as he waits for the next call at his workstation. He says that he never knows what type of call he’ll get next: it might be straightforward, sad, complicated — or a mix.
“You’ve got to be flexible,” he said.
With the newly-awarded three-year contract, the team at Fred Hutch will also be looking at other ways to have a greater impact. They are planning to work with NCI to explore health communications research studies on how they can better impact callers’ health.
Even with the changes, a fundamental challenge that the information specialists face remains all too common.
“Sometimes the answer they seek doesn’t exist,” Gore said. That can be one of the hardest aspects of a cancer diagnosis, a feeling familiar to Gore, who lost her first husband to melanoma 30 years ago when their children were young.
“If I had called the Center back in 1987, they would have done just what they do today — worked with my fears and anxieties and my wanting to know. And they could also have talked to my husband,” she said in the Fred Hutch series “Share Your Story.”
— Molly McElroy / Fred Hutch News Service