Abstract
Accumulating evidence indicates that many human cancers are organized as a cellular hierarchy initiated and maintained by self-renewing cancer stem cells. This cancer stem cell model has been most conclusively established for human acute myeloid leukemia (AML), although controversies still exist regarding the identity of human AML stem cells (leukemia stem cell (LSC)). A major implication of this model is that, in order to eradicate the cancer and cure the patient, the cancer stem cells must be eliminated. Monoclonal antibodies have emerged as effective targeted therapies for the treatment of a number of human malignancies and, given their target antigen specificity and generally minimal toxicity, are well positioned as cancer stem cell-targeting therapies. One strategy for the development of monoclonal antibodies targeting human AML stem cells involves first identifying cell surface antigens preferentially expressed on AML LSC compared with normal hematopoietic stem cells. In recent years, a number of such antigens have been identified, including CD123, CD44, CLL-1, CD96, CD47, CD32, and CD25. Moreover, monoclonal antibodies targeting CD44, CD123, and CD47 have demonstrated efficacy against AML LSC in xenotransplantation models. Hopefully, these antibodies will ultimately prove to be effective in the treatment of human AML.
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Acknowledgements
I would like to acknowledge Mark Chao and Max Jan for critical review of the manuscript and Irv Weissman for support and mentorship. This work was supported in part by a grant from the American Association for Cancer Research. RM holds a Career Award for Medical Scientists from the Burroughs Wellcome Fund. RM has filed the US Patent Application Serial No. 12/321,215 entitled ‘Methods For Manipulating Phagocytosis Mediated by CD47’.
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Majeti, R. Monoclonal antibody therapy directed against human acute myeloid leukemia stem cells. Oncogene 30, 1009–1019 (2011). https://doi.org/10.1038/onc.2010.511
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DOI: https://doi.org/10.1038/onc.2010.511
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