A Fred Hutch and University of Washington team of virologists and bioengineers led by Dr. Keith Jerome has received a $200,000 grant — the first phase of up to $1.5 million in milestone-driven funding over four years — to develop nanocarrier technology to deliver therapies to reservoirs of dormant, HIV-infected cells.
The grant is from the New York-based amfAR, or Foundation for AIDS Research, as part of its “Countdown to a Cure for AIDS” initiative, which aims to achieve the scientific underpinnings of a cure by 2020. The hard-to-reach reservoirs are a key barrier to curing HIV.
Almost immediately upon infection, HIV begins to integrate itself into the DNA of some of the longest-lived cells of the body. There the virus lies dormant, unaffected by the lifesaving antiretroviral drugs that keep actively replicating HIV in check. But stop the medication, and the reservoirs rekindle infection.
Nanocarriers are extremely small particles that can be bioengineered to carry drugs to specific cells while limiting toxicity to other cells. In this case, the nanocarriers will target latently HIV-infected CD4 T cells in fluids and lymphoid tissues. Some of the nanocarriers will deliver latency- reversing agents in keeping with an HIV-cure approach that seeks to “kick,” or reawaken, the dormant virus so that it can then be killed.
What’s most unique about the study underway, said Jerome, is that other nanocarriers will deliver an antiproliferative agent called MMF. The project will test a hypothesis by Fred Hutch’s Dr. Joshua Schiffer, a mathematical modeler in the Vaccine and Infectious Disease Division, and Dr. Florian Hladik, an HIV expert also in VIDD, that slowing the replication rate of latently infected CD4 T cells will decrease the reservoir more rapidly than latency reversal alone.
“[Schiffer’s] mathematical models suggest that if one can slow down the rate of proliferation, one might dramatically speed the decay of the HIV reservoir,” Jerome said. “We have this particle that can get the antiproliferates to the right place and we can test this hypothesis to see if we get a measurable acceleration in decay of the reservoir.”
Schiffer is a co-investigator of the study, as is Hladik of Fred Hutch and UW. Another co-investigator, the UW’s Dr. Kim Woodrow, is a bioengineer who developed the nanoparticles and was critical to designing the proposal. Also on the project are UW microbiologists Drs. Shiu-Lok Hu and Robert Coombs, Fred Hutch statistician Dr. Amalia Magaret and Pharmacokinetics Lab Director Dr. Jeannine McCune, and University of Louisiana-Lafayette pathologist Dr. Francois Villinger.
Jerome is head of UW Virology, director of its Molecular Virology Laboratory and co-director, with Dr. Hans-Peter Kiem, of the Fred Hutch-based defeatHIV research group, which is studying cell and gene therapy and immunotherapy approaches to curing HIV.
— Mary Engel / Fred Hutch News Service
A recent study on cancer survivorship by Fred Hutch scientists has been chosen as one of 10 Research Highlights of 2016 by the National Cancer Institute’s Epidemiology and Genomics Research Program. The study, led by Dr. Eric Chow, examined how serious health outcomes differ between two groups of cancer survivors: those who’d been treated with a transplant of blood-forming stem cells (like a bone marrow transplant), and those who had not.
NCI program staff chose the research highlights from all 2016 publications by program grantees nationwide based on these studies’ potential for impact on science or public health.
The study analyzed health data from nearly 1,800 cancer survivors who had had a transplant, a matched group of nearly 5,500 survivors who had not been treated with transplant, and more than 16,000 people in the general population. The team compared the rates of hospitalization, complications, subsequent cancers and deaths across these groups.
The researchers found that those who had had a transplant were more likely than other cancer survivors to experience certain serious health outcomes several years after their treatment, especially major infections and respiratory problems. Other outcomes were equally as likely in the two groups of survivors; for example, they experienced second cancers at the same rate. Overall, all cancer survivors were more likely than those in the general population to have experienced complications in a major organ system years after treatment.
The researchers recommended that health care providers be aware of the long-term risks associated with a history of this type of transplant so they can provide appropriate care to these patients.
“Direct comparisons of outcomes between transplant survivors and non-transplant survivors has been rare. Thus, our study helps fill in that gap,” said Chow, a cancer survivorship researcher at Fred Hutch, the University of Washington and Seattle Children’s Hospital. “There are national and internationally reviewed guidelines that provide guidance to health care providers on things to watch for in transplant survivors. However, the reasons these survivors have more long-term infections and lung issues remain unclear and deserve more scrutiny.”
The NCI Epidemiology and Genomics Research Program awards more than 240 grants and cooperative agreements every year to support studies in human populations on the factors that affect caner occurrence and outcomes. It currently funds more than 330 active grants around the country, including 18 at Fred Hutch.
— Susan Keown / Fred Hutch News Service
World-renowned breast cancer researcher Dr. Nancy Davidson, vice president and director of the Clinical Research Division at Fred Hutch, has received the 2017 Women in Oncology Award, which is presented annually to three outstanding women in academia, industry and advocacy.
Davidson, who won the award for academia, was honored this week at the second annual PRIMO Meeting in Maui, Hawaii. (PRIMO stands for Practical Recommendations in Immuno & Molecular Oncology.)
Davidson has dedicated her career to the study of cancer biology and treatment. In addition to her role at Fred Hutch, she is president and executive director of Seattle Cancer Care Alliance and is head of the Division of Medical Oncology at the University of Washington. She is also president of the American Association for Cancer Research and past president of the American Society of Clinical Oncology.
Other winners included Kathy Giusti, founder and executive chairman of the Multiple Myeloma Research Foundation and the Multiple Myeloma Research Consortium, who was honored for advocacy; and Jill DeSimone, head of U.S. Oncology at Merck, who was honored for industry.
The Women in Oncology Award, organized by PRIMO Education and Cancer Expert Now, seeks to recognize women who have made outstanding contributions to the lives of those fighting cancer.
— Adapted from SCCA Blog