Acute myeloid leukemia is one of the most common — and aggressive — types of blood cancer that strike adults.
A bone marrow transplant can offer a potential cure. But older patients often can’t handle the heavy rounds of radiation and/or chemotherapy required before the procedure. And many patients — especially those from racial and ethnic minorities — won’t find a fully matched bone marrow donor.
A physician-scientist at Fred Hutchinson Cancer Research Center wants to expand access to these lifesaving treatments by delivering them with a gentler touch. Dr. Johnnie Orozco will use a new five-year, $3.4 million grant from the National Institutes of Health to develop safer, more targeted therapies to treat people with AML.
Orozco will study how to precisely deliver powerful radioactive particles to AML cells in mice while sparing healthy cells and tissues. He will attach those isotopes to antibodies — the same proteins your body makes in response to a virus or disease. These antibodies can home in on a surface marker found on diseased cells, where they will deliver the radioactive payload. Orozco will then combine these “radioimmunotherapy” approaches with novel drugs that can inhibit DNA damage repair and promote cell death.
Orozco will then test the most promising combination candidates before a type of bone marrow transplant that doesn’t require perfectly matched patients and donors. Called a “haploidentical” transplant, these procedures use bone marrow cells that are only half-matched to a patient. Any patient should readily be able to find a haploidentical donor.
This type of transplant has helped expand access to the potentially curative bone marrow transplant for racial and ethnic minorities, whose chances for finding a fully matched donor can be slim, Orozco said. A patient’s likelihood of finding a matching bone marrow donor can vary dramatically depending on ethnic background. According to a report from the National Marrow Donor Program/Be the Match registry, which helps U.S. transplant patients find donors, a white patient of European descent has a 75% chance of finding a matched donor. But a Black patient with Central or South American background only has a 16% chance.
Orozco, a Latino physician-scientist, has always sought to tackle these disparities through his research. According to recent NIH data, only 4% of NIH R01 grants are awarded to Latino principal investigators.
“This is a good example of why we need diverse representation among researchers: so that we can define the research agenda with treatments with the potential to benefit all, especially populations that have been marginalized,” Orozco said. “Hopefully some of the changes from the energy of the current climate will increase representation and promote a change in these statistics for the better.”
Orozco was mentored by the late Dr. Oliver “Ollie” Press, who pioneered the field of radioimmunotherapy. He notes that current and former Fred Hutch researchers like Drs. Brenda Sandmaier, Damian Green, Ajay Gopal and John Pagel have continued to advance radioimmunotherapy work. Orozco will collaborate with them and other scientists across Fred Hutch (Drs. Sandmaier and Roland Walter) and the University of Washington (Drs. Scott Wilbur and Yawen Li from UW Radiation Oncology). This multidisciplinary team has the experience and resources to speed his work into the clinic, Orozco said, given the dozens of clinical trials these investigators have started in the Fred Hutch/University of Washington Cancer Consortium’s clinics.
“There’s no way I could do this by myself,” Orozco said. “At the end of the day, it’s the patients who need cures. We don’t want to publish this stuff just to have it end up in a library. We need to get it to patients, and Seattle is the perfect place to do that.”
Jake Siegel is a former staff writer at Fred Hutchinson Cancer Center. Previously, he covered health topics at UW Medicine and technology at Microsoft. He has an M.A. from the Missouri School of Journalism.