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Published on: March 26, 2018
A radiolabeled antibody targeting CD123(+) leukemia stem cells - initial radioimmunotherapy studies in NOD/SCID mice
Jeffrey V Leyton1, Catherine Gao1, Brent Williams2
1Department of Pharmaceutical Sciences, University of Toronto, Toronto, ON, Canada.
Abstract:
Radioimmunotherapy (RIT) with anti-CD123 monoclonal antibody CSL360 modified with nuclear translocation sequence (NLS) peptides and labeled with the Auger electron-emitter, (111)In ((111)In-NLS-CSL360) was studied in the prevalent NOD/SCID mouse AML engraftment assay. Significant decreases in CD123(+) leukemic cells and impairment of leukemic stem cell self-renewal were achieved with high doses of RIT. However, NOD/SCID mice were very radiosensitive to these doses. At low non-toxic treatment doses, (111)In-NLS-CSL360 demonstrated a trend towards improved survival associated with decreased spleen/body weight ratio, an indicator of leukemia burden, and almost complete eradication of leukemia from the bone marrow in some mice.
