Development of Therapeutic Monoclonal Antibodies to Myeloid Leukemia Cancer Stem Cells
The aim of this proposal is to develop therapeutic monoclonal antibodies specific to the Chronic Myeloid Leukemia (CML) and Acute Myeloid Leukemia (AML) Cancer Stem Cells (CSC). Cancer stem cells arise from normal stem and progenitor cells though a number of gene mutations. CSCs are a small population of cells within the tumor that drives its growth. Most cells in the tumor are derived from the CSC but do not have growth potential. The CSCs are also responsible for the relapse after therapy. Since these cells are very resistant to current chemotherapies, treatment will only be successful if the CSC is directly targeted and eliminated. We have identified several highly specific cell surface targets to CSC which are not on the surface of normal cell types. Monoclonal antibodies will be generated that kill only cells expressing these targets. Due to the limited expression pattern, we believe therapeutic monoclonal antibodies developed to these targets would have less toxicity than current treatments and may offer a cure to these leukemias.
Myeloid leukemias are devastating diseases especially in the elderly who can not tolerate intensive chemotherapeutic treatments. Approximately 3000 cases of myeloid leukemia will be diagnosed in the state of California in 2008 according to National Cancer Institute estimates. With current therapies, the 5 year survival rate for acute myeloid leukemia is 21%. Survival of patients with advanced CML is only 20-40%. Improved cancer treatment would directly benefit the people of California. The aim of this research proposal is to develop therapeutic monoclonal antibodies specific to the acute myeloid leukemia (AML) and chronic myeloid leukemia (CML) cancer stem cells (CSC). CSCs are a rare population of cells within the tumor that are responsible for its growth. CSCs are resistant to chemotherapies and responsible for the reoccurrence of disease following treatment. Monoclonal antibodies bind to and kill only cells expressing a specific target. Development of monoclonal antibodies that bind to and kill only cells expressing a specific target could provide a novel treatment to decrease the relapse and reoccurrence of the diseases.