"Targeting Leukemia Stem Cells
The major goals of STEMTARGET is to identify novel targets on leukemic stem cells (LSCs), generate novel insights into LSC biology, and to initiate the development of LSC-directed therapeutic antibodies. The research will focus on three specific aims: (I) To characterize novel cell surface targets on LSCs, identified by in vivo RNA interference screens. (II) To utilize an in-house developed cytokine screen for identification of cell surface targets selectively important for LSCs. (III) To measure receptor expression in patient samples and demonstrate proof of concept for therapeutic effect with antibody-treatment of leukemic mice.
Background: In adults, AML has a poor prognosis, and novel therapies are needed. In order to be maximally effective, an important goal for the development of novel treatments is to target all leukemia cells with the ability to self renew and maintain the disease indefinitely, a population termed LSCs. During Dr Järås postdoctoral training at Harvard Medical School, Boston, he and coworkers developed a potent in vivo shRNA screen and used it to identify therapeutic targets in LSCs, towards both small molecules and blocking antibodies could be directed. In addition, Dr Järås has developed a cytokine screen for identification of cell surface targets selectively important for LSCs.
In STEMTARGET, Dr Järås and coworkers will perform further shRNA screens and cytokine screens for the identification and characterization of candidate therapeutic targets on LSCs. Monoclonal antibodies targeting identified cell surface targets will be generated and proof of concept experiments for therapeutic targeting will be performed by treating mice with established leukemia. Successful completion of this research program will identify novel targets on LSC, and provide initial validation of therapeutic potential."
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