Cargando…

An agonist antibody prefers relapsed AML for induction of cells that kill each other

Previously, we reported an agonist antibody to a cytokine receptor, Thrombopoietin receptor (TPOR) that effectively induces cytotoxic killer cells from precursor tumor cells isolated from newly diagnosed AML patients. Here, we show that the TPOR agonist antibody can induce even relapsed AML cells in...

Descripción completa

Detalles Bibliográficos
Autores principales: Yea, Kyungmoo, Jones, Teresa M., Jung, Dokyung, Shin, Sanghee, Arlian, Britni M., Han, Kyung Ho, Zha, Zhao, Kim, Minseok S., Oh, Yong-Seok, Zhang, Hongkai, Lerner, Richard A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6401169/
https://www.ncbi.nlm.nih.gov/pubmed/30837591
http://dx.doi.org/10.1038/s41598-019-40087-7
_version_ 1783400111345238016
author Yea, Kyungmoo
Jones, Teresa M.
Jung, Dokyung
Shin, Sanghee
Arlian, Britni M.
Han, Kyung Ho
Zha, Zhao
Kim, Minseok S.
Oh, Yong-Seok
Zhang, Hongkai
Lerner, Richard A.
author_facet Yea, Kyungmoo
Jones, Teresa M.
Jung, Dokyung
Shin, Sanghee
Arlian, Britni M.
Han, Kyung Ho
Zha, Zhao
Kim, Minseok S.
Oh, Yong-Seok
Zhang, Hongkai
Lerner, Richard A.
author_sort Yea, Kyungmoo
collection PubMed
description Previously, we reported an agonist antibody to a cytokine receptor, Thrombopoietin receptor (TPOR) that effectively induces cytotoxic killer cells from precursor tumor cells isolated from newly diagnosed AML patients. Here, we show that the TPOR agonist antibody can induce even relapsed AML cells into killer cells more potently than newly diagnosed AML cells. After stimulation by the agonist antibody, these relapsed leukemic cells enter into a differentiation process of killer cells. The antibody-induced killer cells express, Granzyme B and Perforin that assault and kill other members of the AML cell population. Particularly, the agonist antibody showed potent efficacy on the AML xenograft model in mice using the NOD/LtSz-scid IL2Rγc null (NSG) mice. These results show that the TPOR agonist antibody that induces AML cells to kill each other is effective on both relapsed AML cells and in vivo. Therefore, this study suggests a new strategy for the treatment of cancer relapse after chemotherapy.
format Online
Article
Text
id pubmed-6401169
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher Nature Publishing Group UK
record_format MEDLINE/PubMed
spelling pubmed-64011692019-03-07 An agonist antibody prefers relapsed AML for induction of cells that kill each other Yea, Kyungmoo Jones, Teresa M. Jung, Dokyung Shin, Sanghee Arlian, Britni M. Han, Kyung Ho Zha, Zhao Kim, Minseok S. Oh, Yong-Seok Zhang, Hongkai Lerner, Richard A. Sci Rep Article Previously, we reported an agonist antibody to a cytokine receptor, Thrombopoietin receptor (TPOR) that effectively induces cytotoxic killer cells from precursor tumor cells isolated from newly diagnosed AML patients. Here, we show that the TPOR agonist antibody can induce even relapsed AML cells into killer cells more potently than newly diagnosed AML cells. After stimulation by the agonist antibody, these relapsed leukemic cells enter into a differentiation process of killer cells. The antibody-induced killer cells express, Granzyme B and Perforin that assault and kill other members of the AML cell population. Particularly, the agonist antibody showed potent efficacy on the AML xenograft model in mice using the NOD/LtSz-scid IL2Rγc null (NSG) mice. These results show that the TPOR agonist antibody that induces AML cells to kill each other is effective on both relapsed AML cells and in vivo. Therefore, this study suggests a new strategy for the treatment of cancer relapse after chemotherapy. Nature Publishing Group UK 2019-03-05 /pmc/articles/PMC6401169/ /pubmed/30837591 http://dx.doi.org/10.1038/s41598-019-40087-7 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Yea, Kyungmoo
Jones, Teresa M.
Jung, Dokyung
Shin, Sanghee
Arlian, Britni M.
Han, Kyung Ho
Zha, Zhao
Kim, Minseok S.
Oh, Yong-Seok
Zhang, Hongkai
Lerner, Richard A.
An agonist antibody prefers relapsed AML for induction of cells that kill each other
title An agonist antibody prefers relapsed AML for induction of cells that kill each other
title_full An agonist antibody prefers relapsed AML for induction of cells that kill each other
title_fullStr An agonist antibody prefers relapsed AML for induction of cells that kill each other
title_full_unstemmed An agonist antibody prefers relapsed AML for induction of cells that kill each other
title_short An agonist antibody prefers relapsed AML for induction of cells that kill each other
title_sort agonist antibody prefers relapsed aml for induction of cells that kill each other
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6401169/
https://www.ncbi.nlm.nih.gov/pubmed/30837591
http://dx.doi.org/10.1038/s41598-019-40087-7
work_keys_str_mv AT yeakyungmoo anagonistantibodyprefersrelapsedamlforinductionofcellsthatkilleachother
AT jonesteresam anagonistantibodyprefersrelapsedamlforinductionofcellsthatkilleachother
AT jungdokyung anagonistantibodyprefersrelapsedamlforinductionofcellsthatkilleachother
AT shinsanghee anagonistantibodyprefersrelapsedamlforinductionofcellsthatkilleachother
AT arlianbritnim anagonistantibodyprefersrelapsedamlforinductionofcellsthatkilleachother
AT hankyungho anagonistantibodyprefersrelapsedamlforinductionofcellsthatkilleachother
AT zhazhao anagonistantibodyprefersrelapsedamlforinductionofcellsthatkilleachother
AT kimminseoks anagonistantibodyprefersrelapsedamlforinductionofcellsthatkilleachother
AT ohyongseok anagonistantibodyprefersrelapsedamlforinductionofcellsthatkilleachother
AT zhanghongkai anagonistantibodyprefersrelapsedamlforinductionofcellsthatkilleachother
AT lernerricharda anagonistantibodyprefersrelapsedamlforinductionofcellsthatkilleachother
AT yeakyungmoo agonistantibodyprefersrelapsedamlforinductionofcellsthatkilleachother
AT jonesteresam agonistantibodyprefersrelapsedamlforinductionofcellsthatkilleachother
AT jungdokyung agonistantibodyprefersrelapsedamlforinductionofcellsthatkilleachother
AT shinsanghee agonistantibodyprefersrelapsedamlforinductionofcellsthatkilleachother
AT arlianbritnim agonistantibodyprefersrelapsedamlforinductionofcellsthatkilleachother
AT hankyungho agonistantibodyprefersrelapsedamlforinductionofcellsthatkilleachother
AT zhazhao agonistantibodyprefersrelapsedamlforinductionofcellsthatkilleachother
AT kimminseoks agonistantibodyprefersrelapsedamlforinductionofcellsthatkilleachother
AT ohyongseok agonistantibodyprefersrelapsedamlforinductionofcellsthatkilleachother
AT zhanghongkai agonistantibodyprefersrelapsedamlforinductionofcellsthatkilleachother
AT lernerricharda agonistantibodyprefersrelapsedamlforinductionofcellsthatkilleachother