Cargando…

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(...

Descripción completa

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:
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
_version_ 1782392617107980288
author Leyton, Jeffrey V.
Gao, Catherine
Williams, Brent
Keating, Armand
Minden, Mark
Reilly, Raymond M.
author_facet Leyton, Jeffrey V.
Gao, Catherine
Williams, Brent
Keating, Armand
Minden, Mark
Reilly, Raymond M.
author_sort Leyton, Jeffrey V.
collection PubMed
description 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.
format Online
Article
Text
id pubmed-4588397
institution National Center for Biotechnology Information
language English
publishDate 2015
publisher Elsevier
record_format MEDLINE/PubMed
spelling pubmed-45883972015-10-23 A radiolabeled antibody targeting CD123(+) leukemia stem cells – initial radioimmunotherapy studies in NOD/SCID mice engrafted with primary human AML Leyton, Jeffrey V. Gao, Catherine Williams, Brent Keating, Armand Minden, Mark Reilly, Raymond M. Leuk Res Rep Case Report 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. Elsevier 2015-09-18 /pmc/articles/PMC4588397/ /pubmed/26500848 http://dx.doi.org/10.1016/j.lrr.2015.07.003 Text en © 2015 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Case Report
Leyton, Jeffrey V.
Gao, Catherine
Williams, Brent
Keating, Armand
Minden, Mark
Reilly, Raymond M.
A radiolabeled antibody targeting CD123(+) leukemia stem cells – initial radioimmunotherapy studies in NOD/SCID mice engrafted with primary human AML
title A radiolabeled antibody targeting CD123(+) leukemia stem cells – initial radioimmunotherapy studies in NOD/SCID mice engrafted with primary human AML
title_full A radiolabeled antibody targeting CD123(+) leukemia stem cells – initial radioimmunotherapy studies in NOD/SCID mice engrafted with primary human AML
title_fullStr A radiolabeled antibody targeting CD123(+) leukemia stem cells – initial radioimmunotherapy studies in NOD/SCID mice engrafted with primary human AML
title_full_unstemmed A radiolabeled antibody targeting CD123(+) leukemia stem cells – initial radioimmunotherapy studies in NOD/SCID mice engrafted with primary human AML
title_short A radiolabeled antibody targeting CD123(+) leukemia stem cells – initial radioimmunotherapy studies in NOD/SCID mice engrafted with primary human AML
title_sort radiolabeled antibody targeting cd123(+) leukemia stem cells – initial radioimmunotherapy studies in nod/scid mice engrafted with primary human aml
topic Case Report
url 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
work_keys_str_mv AT leytonjeffreyv aradiolabeledantibodytargetingcd123leukemiastemcellsinitialradioimmunotherapystudiesinnodscidmiceengraftedwithprimaryhumanaml
AT gaocatherine aradiolabeledantibodytargetingcd123leukemiastemcellsinitialradioimmunotherapystudiesinnodscidmiceengraftedwithprimaryhumanaml
AT williamsbrent aradiolabeledantibodytargetingcd123leukemiastemcellsinitialradioimmunotherapystudiesinnodscidmiceengraftedwithprimaryhumanaml
AT keatingarmand aradiolabeledantibodytargetingcd123leukemiastemcellsinitialradioimmunotherapystudiesinnodscidmiceengraftedwithprimaryhumanaml
AT mindenmark aradiolabeledantibodytargetingcd123leukemiastemcellsinitialradioimmunotherapystudiesinnodscidmiceengraftedwithprimaryhumanaml
AT reillyraymondm aradiolabeledantibodytargetingcd123leukemiastemcellsinitialradioimmunotherapystudiesinnodscidmiceengraftedwithprimaryhumanaml
AT leytonjeffreyv radiolabeledantibodytargetingcd123leukemiastemcellsinitialradioimmunotherapystudiesinnodscidmiceengraftedwithprimaryhumanaml
AT gaocatherine radiolabeledantibodytargetingcd123leukemiastemcellsinitialradioimmunotherapystudiesinnodscidmiceengraftedwithprimaryhumanaml
AT williamsbrent radiolabeledantibodytargetingcd123leukemiastemcellsinitialradioimmunotherapystudiesinnodscidmiceengraftedwithprimaryhumanaml
AT keatingarmand radiolabeledantibodytargetingcd123leukemiastemcellsinitialradioimmunotherapystudiesinnodscidmiceengraftedwithprimaryhumanaml
AT mindenmark radiolabeledantibodytargetingcd123leukemiastemcellsinitialradioimmunotherapystudiesinnodscidmiceengraftedwithprimaryhumanaml
AT reillyraymondm radiolabeledantibodytargetingcd123leukemiastemcellsinitialradioimmunotherapystudiesinnodscidmiceengraftedwithprimaryhumanaml