The bottom line is by understanding the immune response to [core-binding factor] AML, we should be able to develop new forms of immunotherapy to protect patients with [core-binding factor] AML from relapse.— Marie Bleakley, MD, PhD
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Marie Bleakley, MD, PhD, a pediatric oncology physician-scientist at Fred Hutchinson Cancer Research Center (Fred Hutch), has received a 2017 Innovative Research Grant in immuno-oncology from Stand Up To Cancer (SU2C). Dr. Bleakley will use the 3-year, $750,000 award to develop T-cell therapies for core-binding factor acute myeloid leukemia (AML).
“The Stand Up To Cancer award means a great deal to me and my research team,” said Dr. Bleakley, an associate member of the Clinical Research Division at Fred Hutch. “It means that we will be able to devote time and resources to a very interesting and promising area of our research, to be creative and focused, and move this translational research project much closer to the clinic, ultimately bringing new immunotherapy to patients with leukemia.”
Core-binding factor AML represents 15% of all cases of AML. It can be cured with chemotherapy, but between 30% and 40% of patients do not reach complete remission or do achieve remission but then relapse.
Dr. Bleakley believes immunotherapy gives new hope to these patients, as immunotherapy with T cells designed to recognize and kill cancer has been highly effective in other blood cancers. The challenge is that most T-cell immunotherapies target proteins on the surface of normal blood cells, as well as the cancerous ones, and such widespread destruction can create severe side effects for patients. Dr. Bleakley’s group is working to develop immunotherapy that targets cancer-specific proteins within the cell, providing a more focused anticancer approach.
They’ve already discovered that the abnormal “fusion” proteins that are found in core-binding factor AML can be recognized by immune T cells isolated from the blood of normal volunteer donors. Now they want to know more about the parts of the protein the T cells respond to, which will provide clues as to how to manipulate T cells to make them “hunt down” and kill cancer.
With the SU2C award, the Fred Hutch scientists will evaluate T-cell immune responses in patients with core-binding factor AML compared with healthy volunteers. The team will identify core-binding factor–specific T cells in patients and study the relationship between those cells and leukemia control, asking the question of whether the T cells help the patients stay in remission.
From there, the researchers hope to design new forms of immunotherapy, including the genetic transfer of natural T-cell receptors into patients’ T cells, allowing them to kill core-binding factor AML, or vaccines to boost the patients’ natural T-cell responses.
“The bottom line is by understanding the immune response to [core-binding factor] AML, we should be able to develop new forms of immunotherapy to protect patients with [core-binding factor] AML from relapse,” Dr. Bleakley concluded. ■