B.Med.Sc, Herbrew University, Jerusalem, Israel
M.D., Herbrew University, Jerusalem, Israel
My main clinical and research interest is improving outcome of hematopoietic cell transplantation (HCT). Allogeneic HCT has the potential to provide long-term survival and even cure in patients with hematological malignancies. Nonetheless, relapse of malignancy after HCT remains a major cause of transplant failure. Patients who develop graft versus-host disease (GVHD) have reduced relapse rates, suggesting that lymphocytes present in engrafted cells can mediate a concurrent therapeutic graft-versus-leukemia (GVL) effect. One strategy to enhance the GVL effect without promoting GVHD in post-HCT patients is to target leukemia-associated antigens with antigen-specific cytotoxic T cells (CTLs). In my current research in collaboration with Drs. Aude Chapuis and Phil Greenberg we transduced donor derived CD8 cytotoxic T cell with lentiviral vercor, which carries a gene that encodes a high affinity WT1-specific T cell receptor (TCR). The zinc finger transcription factor Wilms tumor antigen 1 (WT1) is expressed at 10- to 1000-fold higher concentrations in leukemic cells compared to normal CD34+ cells, and the magnitude of expression correlates with clinical aggressiveness of acute myeloid leukemia (AML), myelodysplastic syndromes (MDSs), and acute lymphoid leukemia (ALL). Thus, T cells that express high affinity WT1-specific TCR may be able to generate an effective and specific GVL with lower risk of GVHD. In order to evaluate the potential anti leukemic effect of those cells, we have designed a clinical trial to determine the safety and function associated with treating patients with high risk or relapsed AML, MDS, and CML after allogeneic HCT by adoptive transfer of donor-derived CD8 T cells genetically-modified to express a high affinity WT1-specific TCR.
Adoptive immunotherapy in patients with AML, MDS, ALL, and CML; phase II studies that evaluate the efficacy of alternative drugs in patients with steroid-resistant acute graft-versus-host disease.