A radiolabeled antibody targeting CD123(+) leukemia stem cells - initial radioimmunotherapy studies in NOD/SCID mice engrafted with primary human AML

Jeffrey V Leyton; Catherine Gao; Brent Williams; Armand Keating; Mark Minden; Raymond M Reilly

doi:10.1016/j.lrr.2015.07.003

A radiolabeled antibody targeting CD123(+) leukemia stem cells - initial radioimmunotherapy studies in NOD/SCID mice engrafted with primary human AML

Leuk Res Rep. 2015 Sep 18;4(2):55-9. doi: 10.1016/j.lrr.2015.07.003. eCollection 2015.

Authors

Jeffrey V Leyton¹, Catherine Gao¹, Brent Williams², Armand Keating³, Mark Minden⁴, Raymond M Reilly⁵

Affiliations

¹ Department of Pharmaceutical Sciences, University of Toronto, Toronto, ON, Canada.
² 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.
³ 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.
⁴ 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.
⁵ 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.

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.

Keywords: 111In; AML; Auger electrons; Leukemia stem cells; Monoclonal antibodies.