Dr. Bleakley is a pediatric oncologist who leads a translational research program that is developing novel immune cell therapies and stem cell transplant approaches for malignancies in children and young adults. Her Seattle laboratory has expertise in the isolation, genetic modification and propagation of T cells that recognize specific antigens, and are also experts in bioinformatics, genetic and molecular techniques employed for antigen discovery, as well as functional analyses of human T cells. They are currently engineering blood stem cell grafts to prevent severe acute and chronic graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (HCT) and modifying T cells with specific T cell receptors (TCRs) to augment their anti-cancer effects.
A major focus is the development and evaluation of T cell immunotherapy for leukemias. One novel TCR- driven immunotherapy targets the leukemia-associated minor histocompatibility antigen, HA-1, and is currently being evaluated for safety and potential efficacy in a phase I clinical trial that is enrolling patients who develop recurrent leukemia after HCT.
Other ongoing research focuses on understanding the targets and mechanisms of the T cell-mediated graft-versus-leukemia effect after allogeneic HCT, and how it relates to GVHD. Recent clinical trials lead by Bleakley’s team are testing stem cell grafts from which a specific (‘naïve”) T cell subset is depleted and are showing very low rates of severe and chronic GVHD and lower rates of relapse than expected. The team is working to understand the mechanism of the anti-leukemic effect in this context.
In addition, the Bleakley lab is evaluating T cell responses to aberrant and/or overexpressed proteins in acute leukemias and other myeloid disorders, including acute myeloid leukemia (AML), MLL (mixed lineage leukemia gene) rearranged AML and acute lymphoblastic leukemia (ALL), and myeloproliferative neoplasms (MPN).