At Fred Hutch News Service, our writers witness daily the excitement of covering new developments in the science of cancer and the human immune system. As 2016 draws to a close, we asked them to sort through the stories about Fred Hutch research they had written this year, and offer our readers a selection of those they felt were most meaningful and important.
Throughout the year, immunotherapy — harnessing the power of the body’s immune system to fight disease — continued to stake its claim as central to the future of cancer research. Fred Hutch’s expertise in the human immune system dates back to the early days of bone marrow transplantation. It has matured over four decades of transplantation research, was expanded in our work against HIV (a virus that destroys the immune system), and is now playing out in promising early clinical trials of CAR T-cell therapies in which disease-fighting white blood cells are genetically modified to kill cancerous cells.
For Hutch News Service writer Susan Keown, one immunotherapy story stood out: a pioneering trial of T-cell therapy against B-cell acute lymphocytic leukemia, or ALL. She profiled patient Kristin Kleinhofer, who in 2014 enrolled in a trial of T cells engineered to fight her cancer. “There were no alternative things to do. It was my last hope at the time,” Kleinhofer said. In April 2016, the investigators leading that immunotherapy trial published their first set of results; Kleinhofer was among the 93 percent of participants who went into complete remission after their T cells were re-engineered into cancer killers — even though multiple other treatments had already failed them.
“In early-phase trials, you’re continually learning. You don’t expect results like these from early-phase trials. That’s why these response rates are so extraordinary,” said senior author Dr. David Maloney. Read the full story.
Immunotherapy also encompasses a raft of new drugs that are designed to overcome the tricks cancer cells employ to shield themselves from the body’s natural defenses. Keown also told the story of Stan Collender, a patient with a rare skin cancer, Merkel cell carcinoma, who is participating in a trial of the drug pembrolizumab, also known as Keytruda. In this small study, led by Hutch researcher Dr. Paul Nghiem, just over half the 26 patients with advanced cancers saw their tumors shrink or disappear after receiving the immune-boosting drug as a first-line systemic therapy. When preliminary results of the trial were first released, said Nghiem, “the field changed overnight.” Read the full story.
Along with the promise of immunotherapy comes a cost: This highly personalized care is extremely expensive. But Fred Hutch researchers are already working on strategies to lower the cost. In October, writer Mary Engel profiled the work of researcher Dr. Jennifer Adair, who is developing “gene therapy in a box.” This simplified, portable technology delivered modified blood stem cells that were as good as — or better — than those manufactured in highly regulated clean rooms and required less than half the staff, according to a study published in Nature Communications. The adapted cells also successfully repopulated the blood system when tested in two different animal models, the authors noted. It hasn’t yet been tested in humans.
The portable device suggests a solution to one of the most vexing challenges of gene therapy: how to make these emerging, high-tech treatments accessible and affordable, moving them beyond a handful of specialized research centers to clinics worldwide.
“We either had to think about how to build million-dollar infrastructure and clean-room facilities in clinics all around the world, which is not feasible, or we had to think about simplifying this process into what I originally envisioned as a black box,” Adair said. "I was so motivated by the problem that it's undertaking — specifically, distribution to places in the world that don’t have any access to this type of therapy now." Read the full story.
Engel regularly covers the Hutch’s global reach, through stories about the work of the HIV Vaccine Trials Network, headquartered at the Hutch. This year has been pivotal for HVTN, which launched two important international trials in the quest for an AIDS vaccine.
In October, in South Africa, HVTN began a large-scale trial of a modified version of the so-called Thai vaccine, which in 2009 became the only one tested so far to show even modest protection against the rapidly mutating virus, which has killed 35 million people worldwide since the HIV/AIDS pandemic began in 1981. The regimen being tested in the new trial has been altered to be more protective, longer-lasting and effective against the predominant HIV subtype in South Africa, which has the largest HIV epidemic in the world. “If an HIV vaccine were found to work in South Africa, it could dramatically alter the course of the pandemic,” said Dr. Glenda Gray, co-director of HVTN and leader of its Africa programs. Government regulators have said they would consider licensing an HIV vaccine if it protects at least 50 percent of those who receive it.
HVTN launched another clinical trial earlier this year on an approach called antibody-mediated prevention, or AMP. Two parallel AMP clinical trials will eventually involve more than 4,000 participants in the United States, South America and southern Africa. Rather than delivering a vaccine, the AMP trial is testing an intravenous infusion to deliver so-called broadly neutralizing antibodies. If the experimental antibodies being tested in the AMP trial provide protection as hoped, information gleaned from the study could help scientists figure out how to reverse-engineer a vaccine to elicit the same antibodies at the concentrations needed. Read the full stories about the modified Thai vaccine and the AMP trial.
Writer Rachel Tompa also explored Fred Hutch’s global impact in an article recently revisited by the New York Times. She tells the story of how leukemia specialist Dr. Jerry Radich and his team developed a method, supported initially by the fundraising bike ride Obliteride, to diagnose chronic myeloid leukemia, or CML, accurately from dried blood spots on special paper. The paper is shipped by “snail mail” — at a tiny fraction of the price of FedEx-ing fresh tubes of blood halfway around the world to clinics that could analyze them. Patients diagnosed with CML in 80 low- and middle-income countries can receive lifetime treatment with Gleevec for free through a partnership with the Max Foundation and drug manufacturer Novartis. “It’s a spectacular gift” for CML patients,” said Radich. Read Tompa’s full story.
Prostate cancer is second only to lung cancer in the number of annual cancer deaths among U.S. men. Two important papers regarding metastatic prostate cancer were published this year by Fred Hutch researcher Dr. Pete Nelson, as reported by writer Sabrina Richards. The first, published in the journal Nature Medicine, showed that though metastases from different patients varied widely in their genetic characteristics, within each individual patient they were remarkably similar. That suggests that metastatic prostate cancer is indeed an appealing target for “precision oncology,” where treatments are tailored to the individual, and that a single biopsy may provide enough information for oncologists to guide such therapy. Read the full story.
A second study, published in the New England Journal of Medicine, showed that men diagnosed with metastatic prostate cancer are five times more likely to harbor inherited mutations in DNA- repair genes, such as the BRCA1 and BRCA2 genes implicated in breast cancer. Screening for these mutations could help men with prostate cancer get more tailored treatment, provide better clarity on their prognosis and alert family members to their own cancer risks. “The implications are big in terms of intercepting and preventing a cancer,” Nelson said. Read the full story.
Diane Mapes reported last March on the release of a major report compiled by a National Academies of Sciences, Engineering and Medicine to set goals for the rapidly emerging field of precision medicine. “Precision medicine just got its playbook,” Mapes explained. “It’s long and complicated and chockablock with buzzwords like big data, biomarker tests, targeted therapies and rapid learning … but the crack team of medical experts who created it believe their recommendations will help guide us all to a healthier future.” The story focuses on the contributions of Fred Hutch researcher Dr. Gary Lyman, who helped develop recommendations for the use of biomarker tests for molecularly targeted therapies. “This is the future of medicine and particularly the future of oncology,” he said. Read the full story.
In another piece, Mapes covered a study on how chemotherapy affects childhood cancer survivors’ ability to have children later in life. The findings were mixed. Women who’d had cancer as kids fared better, for the most part. Seventy percent of survivors had had kids by the age of 45 compared to 80 percent of their healthier sisters. “We think these results will be encouraging for most women who were treated with chemotherapy in childhood,” said study leader Dr. Eric Chow. But there was one caveat: Women who waited until they were over 30 had a slimmer chance of getting pregnant. For male survivors of childhood cancers, the results were not as promising: Only half reported they’d fathered a child (or got a partner pregnant) by age 45 compared to 80 percent of the control group. Read the full story.
Bookmark this link to read more stories from 2016 — and look for those to come in 2017 — that highlight Fred Hutch research.
Writers Sabin Russell, Diane Mapes, Mary Engel, Sabrina Richards, Susan Keown, and Rachel Tompa contributed to this report.