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GMP-Compliant, Large-Scale Expanded Allogeneic Natural Killer Cells Have Potent Cytolytic Activity against Cancer Cells In Vitro and In Vivo

Ex vivo-expanded, allogeneic natural killer (NK) cells can be used for the treatment of various types of cancer. In allogeneic NK cell therapy, NK cells from healthy donors must be expanded in order to obtain a sufficient number of highly purified, activated NK cells. In the present study, we establ...

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Autores principales: Lim, Okjae, Lee, Yuna, Chung, Hyejin, Her, Jung Hyun, Kang, Sang Mi, Jung, Mi-young, Min, Bokyung, Shin, Hyejin, Kim, Tae Min, Heo, Dae Seog, Hwang, Yu Kyeong, Shin, Eui-Cheol
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3543306/
https://www.ncbi.nlm.nih.gov/pubmed/23326467
http://dx.doi.org/10.1371/journal.pone.0053611
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author Lim, Okjae
Lee, Yuna
Chung, Hyejin
Her, Jung Hyun
Kang, Sang Mi
Jung, Mi-young
Min, Bokyung
Shin, Hyejin
Kim, Tae Min
Heo, Dae Seog
Hwang, Yu Kyeong
Shin, Eui-Cheol
author_facet Lim, Okjae
Lee, Yuna
Chung, Hyejin
Her, Jung Hyun
Kang, Sang Mi
Jung, Mi-young
Min, Bokyung
Shin, Hyejin
Kim, Tae Min
Heo, Dae Seog
Hwang, Yu Kyeong
Shin, Eui-Cheol
author_sort Lim, Okjae
collection PubMed
description Ex vivo-expanded, allogeneic natural killer (NK) cells can be used for the treatment of various types of cancer. In allogeneic NK cell therapy, NK cells from healthy donors must be expanded in order to obtain a sufficient number of highly purified, activated NK cells. In the present study, we established a simplified and efficient method for the large-scale expansion and activation of NK cells from healthy donors under good manufacturing practice (GMP) conditions. After a single step of magnetic depletion of CD3(+) T cells, the depleted peripheral blood mononuclear cells (PBMCs) were stimulated and expanded with irradiated autologous PBMCs in the presence of OKT3 and IL-2 for 14 days, resulting in a highly pure population of CD3(−)CD16(+)CD56(+) NK cells which is desired for allogeneic purpose. Compared with freshly isolated NK cells, these expanded NK cells showed robust cytokine production and potent cytolytic activity against various cancer cell lines. Of note, expanded NK cells selectively killed cancer cells without demonstrating cytotoxicity against allogeneic non-tumor cells in coculture assays. The anti-tumor activity of expanded human NK cells was examined in SCID mice injected with human lymphoma cells. In this model, expanded NK cells efficiently controlled lymphoma progression. In conclusion, allogeneic NK cells were efficiently expanded in a GMP-compliant facility and demonstrated potent anti-tumor activity both in vitro and in vivo.
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spelling pubmed-35433062013-01-16 GMP-Compliant, Large-Scale Expanded Allogeneic Natural Killer Cells Have Potent Cytolytic Activity against Cancer Cells In Vitro and In Vivo Lim, Okjae Lee, Yuna Chung, Hyejin Her, Jung Hyun Kang, Sang Mi Jung, Mi-young Min, Bokyung Shin, Hyejin Kim, Tae Min Heo, Dae Seog Hwang, Yu Kyeong Shin, Eui-Cheol PLoS One Research Article Ex vivo-expanded, allogeneic natural killer (NK) cells can be used for the treatment of various types of cancer. In allogeneic NK cell therapy, NK cells from healthy donors must be expanded in order to obtain a sufficient number of highly purified, activated NK cells. In the present study, we established a simplified and efficient method for the large-scale expansion and activation of NK cells from healthy donors under good manufacturing practice (GMP) conditions. After a single step of magnetic depletion of CD3(+) T cells, the depleted peripheral blood mononuclear cells (PBMCs) were stimulated and expanded with irradiated autologous PBMCs in the presence of OKT3 and IL-2 for 14 days, resulting in a highly pure population of CD3(−)CD16(+)CD56(+) NK cells which is desired for allogeneic purpose. Compared with freshly isolated NK cells, these expanded NK cells showed robust cytokine production and potent cytolytic activity against various cancer cell lines. Of note, expanded NK cells selectively killed cancer cells without demonstrating cytotoxicity against allogeneic non-tumor cells in coculture assays. The anti-tumor activity of expanded human NK cells was examined in SCID mice injected with human lymphoma cells. In this model, expanded NK cells efficiently controlled lymphoma progression. In conclusion, allogeneic NK cells were efficiently expanded in a GMP-compliant facility and demonstrated potent anti-tumor activity both in vitro and in vivo. Public Library of Science 2013-01-11 /pmc/articles/PMC3543306/ /pubmed/23326467 http://dx.doi.org/10.1371/journal.pone.0053611 Text en © 2013 Lim et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Lim, Okjae
Lee, Yuna
Chung, Hyejin
Her, Jung Hyun
Kang, Sang Mi
Jung, Mi-young
Min, Bokyung
Shin, Hyejin
Kim, Tae Min
Heo, Dae Seog
Hwang, Yu Kyeong
Shin, Eui-Cheol
GMP-Compliant, Large-Scale Expanded Allogeneic Natural Killer Cells Have Potent Cytolytic Activity against Cancer Cells In Vitro and In Vivo
title GMP-Compliant, Large-Scale Expanded Allogeneic Natural Killer Cells Have Potent Cytolytic Activity against Cancer Cells In Vitro and In Vivo
title_full GMP-Compliant, Large-Scale Expanded Allogeneic Natural Killer Cells Have Potent Cytolytic Activity against Cancer Cells In Vitro and In Vivo
title_fullStr GMP-Compliant, Large-Scale Expanded Allogeneic Natural Killer Cells Have Potent Cytolytic Activity against Cancer Cells In Vitro and In Vivo
title_full_unstemmed GMP-Compliant, Large-Scale Expanded Allogeneic Natural Killer Cells Have Potent Cytolytic Activity against Cancer Cells In Vitro and In Vivo
title_short GMP-Compliant, Large-Scale Expanded Allogeneic Natural Killer Cells Have Potent Cytolytic Activity against Cancer Cells In Vitro and In Vivo
title_sort gmp-compliant, large-scale expanded allogeneic natural killer cells have potent cytolytic activity against cancer cells in vitro and in vivo
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3543306/
https://www.ncbi.nlm.nih.gov/pubmed/23326467
http://dx.doi.org/10.1371/journal.pone.0053611
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