Clinical Expertise
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.
Laboratory Studies
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.