Dr. David Maloney has been appointed the first medical director for cellular immunotherapy at Fred Hutch and the Immunotherapy Clinic at Seattle Cancer Care Alliance, which welcomed its first patient earlier this week.
Maloney is an immunotherapy researcher and blood cancer physician at Fred Hutchinson Cancer Research Center, SCCA and the University of Washington. Maloney also holds the Leonard and Norma Klorfine Endowed Chair for Clinical Research at Fred Hutch.
In his role as medical director for cellular immunotherapy at the Hutch, Maloney will have oversight of critical clinical trials infrastructure and provide expertise for effective research operations. As medical director of the new Immunotherapy Clinic, Maloney will lead the clinic’s physicians and oversee the research and patient care in the clinic.
Maloney played a key role in the development of the Immunotherapy Clinic, the only one of its kind in the nation. Designed to meet the needs of patients participating in cellular immunotherapy clinical trials, the facility will have a formal grand opening later this year at SCCA, the treatment arm of Fred Hutch.
Maloney’s career has encompassed research on several different types of immunotherapies. He was part of the Stanford team that discovered antibodies (immune system proteins) that target lymphoma cells could be generated and delivered to patients as a cancer-specific therapy. This discovery led Dr. Maloney to the initial development of the molecule known as rituximab, now a standard blood cancer therapy.
After arriving at the Hutch in 1994, he joined Drs. Rainer Storb and Brenda Sandmaier and their team in pioneering non-myeloablative, or mini, transplants, extending the therapeutic power of transplantation to many more patients and demonstrating the power of immune cells to eradicate cancer. Today, Dr. Maloney and colleagues are advancing research on genetically re-engineered T cells, called CAR T cells, in the treatment of certain advanced blood cancers.
— Adapted from Fred Hutch and SCCA releases
When a once-promising HIV vaccine candidate failed completely in a global trial three years ago, scientists set out at once to figure out why. Last year came a surprising and plausible answer: immune system interference from common bacteria in the human gut — our microbiome.
For Dr. Jim Kublin, who helped oversee that trial as executive director of the HIV Vaccine Trials Network, based at Fred Hutch, the failure was deeply disappointing. The trial, known as HTVN 505, was abruptly halted in 2013 after an early peek at results showed the candidate vaccine did not protect study volunteers against infection. But the discovery that communities of gut bugs could profoundly alter response to a vaccine was a revelation.
Now, Kublin and his team of researchers at Fred Hutch’s Vaccine and Infectious Disease Division have received a five-year grant from the federal government to study exactly how the microbiome interacts with the immune system’s responses to vaccines. The grant awarded by the National Institute of Allergy and Infectious Diseases will reach a total of nearly $4 million by the end of the five-year period.
Although the immediate focus of the grant is on HIV vaccines, the work may be pertinent to the microbiome’s role in all kinds of vaccines. “I am really excited about this project,” Kublin said. “It could take us considerably beyond what we’re focused on as the specific aim of this grant.”
In 2015, a team of researchers led by Dr. Barton Haynes of Duke Medicine reported evidence that HVTN 505 may have failed because a component of that vaccine essentially stirred up the wrong antibody response. Antibodies are proteins that our immune system generates to zero in on features atop the surface of invading microbes, blocking their activity or killing them outright. But instead of producing antibodies against HIV, the vaccine stirred up antibodies against similarly structured features on bacteria commonly acquired in the human gut during early childhood, and those antibodies offered no protection against the virus that causes AIDS.
At the start of the study, Kublin’s team — which includes researchers at the University of Washington — will use gene sequencing to identify thousands of different gut bacteria in stool samples taken from vaccine study volunteers. That information will be matched against data collected that measures the various immune reactions these volunteers had in response to vaccines.
Later, the study will use mice with precisely calibrated communities of gut bacteria, drawn from those human volunteers, to see in a highly controlled way how these different varieties of bugs influence responses to HIV vaccines. Another arm of the study will use these mice, with their carefully monitored microbiomes, to study interactions with different immune-stimulating molecules, called adjuvants, which are often added to vaccines to boost effectiveness.
These experiments will gather vast amounts of data. Computer analysis of these data may reveal why some vaccines, or vaccine components, are effective in one person and less so for another. The goal is to find better strategies for fine-tuning the immune responses to future vaccines. “We’re going to be looking at close to a dozen different vaccines,” Kublin said. “We will correlate immune-response data with hundreds of species of bacteria. This is a ‘big data’ analytical challenge.”
— Sabin Russell / Fred Hutch News Service