Monoclonal Antibody Therapy Blocks Leukemia Stem Cells

To eliminate LSCs investigators at the University of New South Wales (Sydney, Australia) took advantage of an earlier finding that the protein CD123, a component of the interleukin-3 receptor, is highly expressed on LSCs but not on normal blood cells. They developed a specific monoclonal antibody directed at CD123.

Results published in the July 2, 2009, issue of the journal Cell Stem Cell revealed that treatment of nonobese diabetic/severe-combined immunodeficient (NOD/SCID) mice with the 7G3 antibody blocked cytokine signaling in transplanted human AML cells. The antibody disrupted migration of the LSCs to bone marrow and activated the animal's innate immune system to destroy the cancer cells.

"Previous research has suggested that leukemia stem cells (LSCs) may lie at the heart of post-treatment relapse and chemoresistance," said senior author Dr. Richard Lock, head of the leukemia biology program at the University of New South Wales. "The recent characterization of defined populations of cancer stem cells in a range of human malignancies, as well as their relative resistance to conventional chemotherapy and radiotherapy, supports the broad applicability of our approach and provides rationale for the progression of AML-LSC-targeted therapeutics from preclinical evaluation to clinical trials."

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University of New South Wales