Bachelor of Medicine & Surgery/MD, 1994:
Flinders University of South Australia, South Australia
Master of Medical Science (M.MSC.) in Clinical Epidemiology, 2000:
The University of Newcastle, New South Wales, Australia
The University of Sydney, New South Wales, Australia
Residency, Pediatrics, 1996-1999:The Children’s Hospital at Westmead, New South Wales, Australia
1. Pediatric Oncology, 1999-2001:
The Children’s Hospital at Westmead, New South Wales, Australia
2. Pediatric Hematology-Oncology, 2002-2005:
Fred Hutchinson Cancer Research Center and Seattle Children’s Hospital
Dr. Bleakley is a pediatric oncologist with expertise in hematopoietic (blood-forming) stem cell transplantation (HCT) to treat leukemia. The blood stem cells that are engrafted in donor (allogenic) HCT can be collected from bone marrow, peripheral blood or umbilical cord blood. T cells which are also present in the stem cell graft are a major part of the curative power of transplantation, but can also cause serious side-effects known as Graft-Versus-Host-Disease (GVHD). Dr. Bleakley is developing ways to optimize the use of T cells in transplantation and cell therapies given after transplantation to prevent and treat relapse of leukemia and other complications. .
Her research is focused on improving outcomes for patients with high-risk leukemia by developing new strategies that optimize the activities of T cells in the context of HCT. In particular, she is working to promote the advantageous Graft-Versus-Leukemia (GVL) effect and reduce the potentially dangerous GVHD that also can be caused by donor T cells after allogeneic transplantation.
T cells act by targeting specific proteins (antigens) on other 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 expressed on leukemia that can be exploited as targets for vaccination and adoptive immunotherapy. She and her laboratory have already identified and characterized five novel human minor H antigens.
Dr. Bleakley’s lab is preparing for a clinical trial using minor H antigen specific T cells to treat recurrent leukemia after transplantation. For this first clinical trial, she chose as a target the ‘gold standard’ highly hematopoietic-restricted minor H antigen, HA-1. The lab members have 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 transduced CD4+ and CD8+ T cells in preparation for a the TCR, gene modified-T cell immunotherapy trial.
Another strategy to prevent GVHD involves selectively removing GVHD-promoting T cells from hematopoietic stem cell grafts. An ongoing set of clinical trials was informed by laboratory studies which showed that a subset of allogeneic donor bone marrow (memory T cells, TM) could be purified and administered to produce immunity to a infections and tumor antigens, with little or no GVHD. The strategy involves removing another, potentially damaging subset of T cells (CD45RA+ naïve T cells, TN).
Dr. Bleakley is currently serving as the Principal Investigator of three clinical trials of TN -depletion for recipients of peripheral blood stem cell grafts (PBMC). The first of these studies has been completed for patients with acute leukemia and HLA-matched related donors. Dr. Bleakley and colleagues showed that TN-depleted PBSC grafts produced rapid immune reconstitution and transfer of pathogen-specific immunity, with a marked reduction of chronic GVHD relative to T cell replete HCT. Moreover, the duration of required immunosuppression after TN-depleted HCT was considerably shorter than with T cell replete HCT, providing a greatly improved platform for immunotherapy. Ultimately, Dr. Bleakley plans to bring together this graft engineering for GVHD prevention in HCT, and T cell immunotherapies following transplantation, along with anti-tumor vaccination to develop a comprehensive treatment approach for patients with high-risk hematologic malignancies.
Ongoing trials, open to patients, include:
A Multi-center Phase II Study of Selective Depletion of CD45RA+ T Cells From Allogeneic Peripheral Blood Stem Cell Grafts for the Prevention of GVHD
A Phase II Study of Selective Depletion of CD45RA+ T Cells From Allogeneic Peripheral Blood Stem Cell Grafts for the Prevention of GVHD in Children