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Nanoparticle T cell engagers for the treatment of acute myeloid leukemia

Acute myeloid leukemia (AML) is the most common type of leukemia and has a 5-year survival rate of 25%. The standard-of-care for AML has not changed in the past few decades. Promising immunotherapy options are being developed for the treatment of AML; yet, these regimens require highly laborious and...

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Autores principales: Alhallak, Kinan, Sun, Jennifer, Muz, Barbara, Jeske, Amanda, Yavner, Jessica, Bash, Hannah, Park, Chaelee, Lubben, Berit, Adebayo, Ola, Achilefu, Samuel, DiPersio, John F., Azab, Abdel Kareem
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8448516/
https://www.ncbi.nlm.nih.gov/pubmed/34548905
http://dx.doi.org/10.18632/oncotarget.28054
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author Alhallak, Kinan
Sun, Jennifer
Muz, Barbara
Jeske, Amanda
Yavner, Jessica
Bash, Hannah
Park, Chaelee
Lubben, Berit
Adebayo, Ola
Achilefu, Samuel
DiPersio, John F.
Azab, Abdel Kareem
author_facet Alhallak, Kinan
Sun, Jennifer
Muz, Barbara
Jeske, Amanda
Yavner, Jessica
Bash, Hannah
Park, Chaelee
Lubben, Berit
Adebayo, Ola
Achilefu, Samuel
DiPersio, John F.
Azab, Abdel Kareem
author_sort Alhallak, Kinan
collection PubMed
description Acute myeloid leukemia (AML) is the most common type of leukemia and has a 5-year survival rate of 25%. The standard-of-care for AML has not changed in the past few decades. Promising immunotherapy options are being developed for the treatment of AML; yet, these regimens require highly laborious and sophisticated techniques. We create nanoTCEs using liposomes conjugated to monoclonal antibodies to enable specific binding. We also recreate the bone marrow niche using our 3D culture system and use immunocompromised mice to enable use of human AML and T cells with nanoTCEs. We show that CD33 is ubiquitously present on AML cells. The CD33 nanoTCEs bind preferentially to AML cells compared to Isotype. We show that nanoTCEs effectively activate T cells and induce AML killing in vitro and in vivo. Our findings suggest that our nanoTCE technology is a novel and promising immuno-therapy for the treatment of AML and provides a basis for supplemental investigations for the validation of using nanoTCEs in larger animals and patients.
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spelling pubmed-84485162021-09-20 Nanoparticle T cell engagers for the treatment of acute myeloid leukemia Alhallak, Kinan Sun, Jennifer Muz, Barbara Jeske, Amanda Yavner, Jessica Bash, Hannah Park, Chaelee Lubben, Berit Adebayo, Ola Achilefu, Samuel DiPersio, John F. Azab, Abdel Kareem Oncotarget Research Paper Acute myeloid leukemia (AML) is the most common type of leukemia and has a 5-year survival rate of 25%. The standard-of-care for AML has not changed in the past few decades. Promising immunotherapy options are being developed for the treatment of AML; yet, these regimens require highly laborious and sophisticated techniques. We create nanoTCEs using liposomes conjugated to monoclonal antibodies to enable specific binding. We also recreate the bone marrow niche using our 3D culture system and use immunocompromised mice to enable use of human AML and T cells with nanoTCEs. We show that CD33 is ubiquitously present on AML cells. The CD33 nanoTCEs bind preferentially to AML cells compared to Isotype. We show that nanoTCEs effectively activate T cells and induce AML killing in vitro and in vivo. Our findings suggest that our nanoTCE technology is a novel and promising immuno-therapy for the treatment of AML and provides a basis for supplemental investigations for the validation of using nanoTCEs in larger animals and patients. Impact Journals LLC 2021-09-14 /pmc/articles/PMC8448516/ /pubmed/34548905 http://dx.doi.org/10.18632/oncotarget.28054 Text en Copyright: © 2021 Alhallak et al. https://creativecommons.org/licenses/by/3.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/3.0/) (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Alhallak, Kinan
Sun, Jennifer
Muz, Barbara
Jeske, Amanda
Yavner, Jessica
Bash, Hannah
Park, Chaelee
Lubben, Berit
Adebayo, Ola
Achilefu, Samuel
DiPersio, John F.
Azab, Abdel Kareem
Nanoparticle T cell engagers for the treatment of acute myeloid leukemia
title Nanoparticle T cell engagers for the treatment of acute myeloid leukemia
title_full Nanoparticle T cell engagers for the treatment of acute myeloid leukemia
title_fullStr Nanoparticle T cell engagers for the treatment of acute myeloid leukemia
title_full_unstemmed Nanoparticle T cell engagers for the treatment of acute myeloid leukemia
title_short Nanoparticle T cell engagers for the treatment of acute myeloid leukemia
title_sort nanoparticle t cell engagers for the treatment of acute myeloid leukemia
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8448516/
https://www.ncbi.nlm.nih.gov/pubmed/34548905
http://dx.doi.org/10.18632/oncotarget.28054
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