Novel targeted and immunotherapeutic strategies in chronic myeloid leukemia.

Overview

The advanced understanding of the molecular biology and immunology of chronic myeloid leukemia (CML) has led to novel therapeutic strategies unique to this disease. CML responds to immune-mediated therapies, including stem cell transplantation, donor lymphocyte infusion (DLI), and interferon alfa. T cells and other immune effectors are implicated in the mechanisms of action of these immune therapies. Recently, clinical observations supported by laboratory data have demonstrated the presence of CML-specific T cells in patients. Several proteins may potentially act as leukemia-specific antigens for major histocompatibility complex (MHC)-restricted cytotoxicity in CML, and active specific therapies (vaccines) are in development. Antigens under investigation include bcr-abl, PR1, Wilms tumor protein (WT1), minor histocompatibility antigens (mH), CML-66, CML-28, and survivin. Other strategies target vascular endothelial growth factor (VEGF) and heat shock protein 90 (Hsp90) inhibitors or make use of CML-derived dendritic cells (DC).