A radiolabeled antibody targeting CD123(+) leukemia stem cells - initial radioimmunotherapy studies in NOD/SCID mice engrafted with primary human AML.
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.
Department of Pharmaceutical Sciences, University of Toronto, Toronto, ON, Canada.
Jeffrey V
JV
Leyton
Department of Pharmaceutical Sciences, University of Toronto, Toronto, ON, Canada.
Catherine
C
Gao
Institute of Medical Science, University of Toronto, Toronto, ON, Canada ; Division of Hematology-Oncology, The Hospital for Sick Children, Toronto, ON, Canada ; Cell Therapy Program, The Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
Brent
B
Williams
Cell Therapy Program, The Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada ; Department of Hematology-Oncology, The Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
Armand
A
Keating
Department of Hematology-Oncology, The Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada ; Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada.
Mark
M
Minden
Department of Pharmaceutical Sciences, University of Toronto, Toronto, ON, Canada ; Toronto General Research Institute, University Health Network, Toronto, ON, Canada ; Joint Department of Medical Imaging, University Health Network, Toronto, ON, Canada.
Raymond M
RM
Reilly
111In; AML; Auger electrons; Leukemia stem cells; Monoclonal antibodies