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(...

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Detalles Bibliográficos
Autores principales: Leyton, Jeffrey V., Gao, Catherine, Williams, Brent, Keating, Armand, Minden, Mark, Reilly, Raymond M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2015
Materias:
Case Report
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4588397/
https://www.ncbi.nlm.nih.gov/pubmed/26500848
http://dx.doi.org/10.1016/j.lrr.2015.07.003
Descripción
Sumario: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.

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