Translational Science and Therapeutics Division, Fred Hutch
Director, Cellular Therapy and Transplantation for Pediatric Leukemia
Gerdin Family Endowed Chair for Leukemia Research
Dr. Marie Bleakley is a pediatric hematologist-oncologist who specializes in hematopoietic (blood-forming) stem cell transplantation and T cell immunotherapy for patients with leukemia and other blood cancers. Her research goal is to develop novel therapies that can optimize the cancer-fighting power of immune T cells while reducing a potentially dangerous side effect known as graft-vs.-host disease, or GVHD. Dr. Bleakley and her team have already pioneered one novel transplantation approach that selectively removes donor T cells that might cause GVHD. They are also genetically engineering T cell therapies that target unique markers to kill a patient’s cancer cells even more effectively.
University of Washington School of Medicine
Fred Hutchinson Cancer Center
Seattle Children's Hospital
PhD, The University of Sydney, 2010
Fellowship, Pediatric Hematology-Oncology, Fred Hutchinson Cancer Center and Seattle Children’s Hospital, 2002-2005
Fellowship, Pediatric Oncology, The Children’s Hospital at Westmead, 1999-2001
MMSC, Clinical Epidemiology, The University of Newcastle, 2000
Residency, Pediatrics, The Children’s Hospital at Westmead, 1996-1999
Bachelor of Medicine & Surgery/MD, Flinders University of South Australia, 1994
Dr. Bleakley specializes in hematopoietic stem cell transplantation (HCT) and T cell immunotherapy for the treatment of leukemia relapse in children. She is developing ways to optimize the use of T cells in transplantation for patients with leukemia and other blood cancers and in targeted T-cell therapies for patients with a variety of cancer diagnoses.
T cells act by targeting specific proteins (antigens) on diseased cells, using highly specialized molecular complexes, called T cell receptors (TCRs). Dr. Bleakley is advancing one strategy that manipulates donor T cell responses to a group of antigens called minor histocompatibility (H) antigens. She established a new technique for isolating and expanding minor H antigen-specific T cells, which is now used for discovering novel hematopoietic-restricted minor H antigens that are expressed on leukemia and can be exploited as targets for vaccination and adoptive immunotherapy. She and her laboratory have already identified and characterized several novel human minor H antigens.
Dr. Bleakley’s team is conducting a clinical trial using minor H antigen specific T cells to treat recurrent leukemia after HCT. For this first clinical trial, she chose as a target the ‘gold standard’ highly hematopoietic-restricted minor H antigen, HA-1. This T cell immunotherapy was developed in her lab, where the team isolated HA-1-specific T cells, sequenced their TCRs, cloned several HA-1 TCRs into lentiviral vectors and evaluated the function of HA-1 TCR-engineered CD4+ and CD8+ T cells.
T cells can have potent therapeutic effects against leukemia and other cancers. However, they can also cause complications after HCT, including graft-versus-host disease. A strategy to prevent GVHD involves selectively removing GVHD-promoting T cells from hematopoietic stem cell grafts. Dr. Bleakley is leading an ongoing set of clinical trials that was informed by laboratory studies, which showed that ‘naïve T cells’ cause severe GVHD while another subset of allogeneic donor T cells (known as ‘memory’ T cells) can be purified and administered to produce immunity to infections and tumors, with little or no GVHD.
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