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

Leukemia Research Reports (Jan 2015)

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

Affiliations

Jeffrey V. Leyton: Department of Pharmaceutical Sciences, University of Toronto, Toronto, ON, Canada
Catherine Gao: Department of Pharmaceutical Sciences, University of Toronto, Toronto, ON, Canada
Brent Williams: Institute of Medical Science, University of Toronto, Toronto, ON, Canada
Armand Keating: Cell Therapy Program, The Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada
Mark Minden: Department of Hematology-Oncology, The Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada
Raymond M. Reilly: Department of Pharmaceutical Sciences, University of Toronto, Toronto, ON, Canada

DOI: https://doi.org/10.1016/j.lrr.2015.07.003
Journal volume & issue: Vol. 4, no. 2
pp. 55 – 59

Abstract

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Radioimmunotherapy (RIT) with anti-CD123 monoclonal antibody CSL360 modified with nuclear translocation sequence (NLS) peptides and labeled with the Auger electron-emitter, 111In (111In-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, 111In-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.

Published in Leukemia Research Reports

ISSN: 2213-0489 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Medicine: Internal medicine: Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Website: http://www.journals.elsevier.com/leukemia-research-reports/

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