Extending its standing as one of the top leukemia programs in the United States, Washington University School of Medicine in St. Louis has been awarded an $11.5 million grant to further high-level investigations into leukemia and related blood cancers.
The grant, from the National Institutes of Health (NIH), funds a prestigious Specialized Program in Research Excellence (SPORE) in leukemia. Washington University is one of only three academic centers in the U.S. to receive this grant.
The National Cancer Institute’s (NCI) SPORE program is intended to boost translational research, connecting promising discoveries in the lab with clinical researchers caring for cancer patients who potentially could benefit from such treatments.
“The program is designed to speed translational research, helping move cutting-edge discoveries into patient care,” said principal investigator Daniel C. Link, MD, the Alan A. and Edith L. Wolff Professor of Medicine. “We hope to build on the successes that came in the first five years of our original SPORE grant,” added Link, who treats patients at Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine.
The goal of the SPORE in leukemia at Washington University is to develop biomarkers and treatments for leukemia and myelodysplastic syndromes and to develop and promote innovative translational leukemia research. Some important progress from the first grant included the development of a new type of immunotherapy utilizing what are called natural killer cells; a new type of inhibitor therapy for myelodysplastic syndrome; and the identification of drugs that inhibit CXCR4, a chemokine receptor, that is highly active against T-cell acute lymphoblastic leukemia. A number of clinical trials based on these and other advances are currently underway.
The SPORE renewal supports five projects, including clinical trials of new treatments for different types of leukemia.
- One project will build on the observation that AML carrying mutations of TP53, which historically carry a very poor prognosis, respond to decitabine, a type of chemotherapy. The researchers will test whether decitabine combined with stem cell transplantation will improve outcomes for this very high risk subset of AML. This project is led by Timothy J. Ley, MD, the Lewis T. and Rosalind B. Apple Professor of Medicine; and John S. Welch, MD, PhD, an associate professor of medicine.
- A second project is aimed at seeking new therapies for a type of cancer — T cell acute lymphoblastic leukemia (T-ALL) — that has no targeted treatments. The project includes a clinical trial of a new inhibitor called BL-8040 in combination with chemotherapy for patients whose leukemia does not respond to standard treatment or has returned after initial therapy. This project is led by Link and Geoffrey L. Uy, MD, an associate professor of medicine.
- A third project involves investigating potential treatments for myelodysplastic syndrome (MDS), a group of cancerous disorders characterized by dysfunctional blood cells. This project will focus on ways to treat MDS and other myeloid cancer cells that contain genetic errors called splicing factor mutations. Drugs called ATR inhibitors may help such patients, according to the project’s lead investigators, Timothy A. Graubert MD, of Harvard Medical School; and Matthew J. Walter, MD, a professor of medicine at Washington University.
- A fourth project is aimed at harnessing immunotherapy against cancer, investigating what are called bi-specific antibodies against AML. In this approach, the antibody binds to both a healthy T cell and a cancerous leukemia cell, bringing the two together so that the T cell can do its job killing the leukemia cell more effectively. This project is led by John F. DiPersio, MD, PhD, the Virginia E. and Sam J. Golman Professor of Medicine; and Michael Rettig, PhD, an associate professor of medicine.
- A fifth project is focused on training a different part of the immune system to recognize cancer, activating a type of immune cell called natural killer cells, and then making them more effective at finding and destroying cancer cells. This project is led by Todd Fehniger, MD, PhD, an associate professor of medicine, and Amanda F. Cashen, MD, an associate professor of medicine.
The SPORE grant also provides funding for administrative support, resources in biostatistics, and infrastructure for the processing of biospecimens, such as tumor samples, with patient permission. The program also helps with career development, supporting the recruitment and mentorship of new investigators in translational leukemia research. In addition, the program has a route for funding pilot studies, providing small grants to support innovative ideas that are not yet ready for the clinic but that show enough potential to be pursued further.
“This SPORE renewal gives us resources to test new therapies for leukemia and develop the next generation of leukemia researchers,” Link said. “This type of environment — that includes career support and funding for research at every stage of the process — is where we think important breakthroughs in cancer care are most likely to happen.”