Cell stem cell, 2009-07, Vol.5 (1), p.31-42
2009
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- Autor(en) / Beteiligte
- Titel
- Monoclonal Antibody-Mediated Targeting of CD123, IL-3 Receptor α Chain, Eliminates Human Acute Myeloid Leukemic Stem Cells
- Ist Teil von
- Cell stem cell, 2009-07, Vol.5 (1), p.31-42
- Ort / Verlag
- Cambridge, MA: Elsevier Inc
- Erscheinungsjahr
- 2009
- Quelle
- Free E-Journal (出版社公開部分のみ）
- Beschreibungen/Notizen
- Leukemia stem cells (LSCs) initiate and sustain the acute myeloid leukemia (AML) clonal hierarchy and possess biological properties rendering them resistant to conventional chemotherapy. The poor survival of AML patients raises expectations that LSC-targeted therapies might achieve durable remissions. We report that an anti-interleukin-3 (IL-3) receptor α chain (CD123)-neutralizing antibody (7G3) targeted AML-LSCs, impairing homing to bone marrow (BM) and activating innate immunity of nonobese diabetic/severe-combined immunodeficient (NOD/SCID) mice. 7G3 treatment profoundly reduced AML-LSC engraftment and improved mouse survival. Mice with pre-established disease showed reduced AML burden in the BM and periphery and impaired secondary transplantation upon treatment, establishing that AML-LSCs were directly targeted. 7G3 inhibited IL-3-mediated intracellular signaling of isolated AML CD34+CD38− cells in vitro and reduced their survival. These results provide clear validation for therapeutic monoclonal antibody (mAb) targeting of AML-LSCs and for translation of in vivo preclinical research findings toward a clinical application.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1934-5909eISSN: 1875-9777DOI: 10.1016/j.stem.2009.04.018Titel-ID: cdi_proquest_miscellaneous_67446684
- Format
- –
- Schlagworte
- Adult, Aged, Aged, 80 and over, Animals, Antibodies, Monoclonal - pharmacology, Antibodies, Monoclonal - therapeutic use, Antigens, CD34 - metabolism, Biological and medical sciences, Bone Marrow - metabolism, Cell Line, Cell Movement - drug effects, Cell Proliferation - drug effects, Cell receptors, Cell structures and functions, Female, Fundamental and applied biological sciences. Psychology, Hematologic and hematopoietic diseases, Hematopoietic Stem Cells - metabolism, Humans, Interleukin-3 Receptor alpha Subunit - antagonists & inhibitors, Interleukin-3 Receptor alpha Subunit - immunology, Intracellular Signaling Peptides and Proteins - metabolism, Leukemia, Myeloid, Acute - immunology, Leukemia, Myeloid, Acute - therapy, Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis, Male, Medical sciences, Mice, Mice, Inbred NOD, Mice, SCID, Middle Aged, Miscellaneous, Molecular and cellular biology, Neoplastic Stem Cells - drug effects, Neoplastic Stem Cells - metabolism, Stem Cell Transplantation, STEMCELL, Transplantation, Heterologous, Tumor Burden