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Cytotoxic effects of ex vivo-expanded natural killer cell-enriched lymphocytes (MYJ1633) against liver cancer

BACKGROUND: Adoptive transfer of immune cells such as T cells and natural killer (NK) cells has emerged as a targeted method of controlling the immune system against cancer. Despite their significant therapeutic potential, efficient methods to generate adequate numbers of NK cells are lacking and ex...

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Autores principales: Choi, Jung-Won, Lee, Eui Soo, Kim, Se Young, Park, Su Il, Oh, Sena, Kang, Jung Hwa, Ryu, Hyun Aae, Lee, Seahyoung
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6700835/
https://www.ncbi.nlm.nih.gov/pubmed/31426763
http://dx.doi.org/10.1186/s12885-019-6034-1
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author Choi, Jung-Won
Lee, Eui Soo
Kim, Se Young
Park, Su Il
Oh, Sena
Kang, Jung Hwa
Ryu, Hyun Aae
Lee, Seahyoung
author_facet Choi, Jung-Won
Lee, Eui Soo
Kim, Se Young
Park, Su Il
Oh, Sena
Kang, Jung Hwa
Ryu, Hyun Aae
Lee, Seahyoung
author_sort Choi, Jung-Won
collection PubMed
description BACKGROUND: Adoptive transfer of immune cells such as T cells and natural killer (NK) cells has emerged as a targeted method of controlling the immune system against cancer. Despite their significant therapeutic potential, efficient methods to generate adequate numbers of NK cells are lacking and ex vivo-expansion and activation of NK cells is currently under intensive investigation. The primary purpose of this study was to develop an effective method for expansion and activation of the effector cells with high proportion of NK cells and increasing cytotoxicity against liver cancer in a short time period. METHODS: Expanded NK cell-enriched lymphocytes (NKL) designated as “MYJ1633” were prepared by using autologous human plasma, cytokines (IL-2, IL-12 and IL-18) and agonistic antibodies (CD16, CD56 and NKp46) without an NK cell-sorting step. The characteristics of NKL were compared to those of freshly isolated PBMCs. In addition, the cytotoxic effect of the NKL on liver cancer cell was examined in vitro and in vivo. RESULTS: The total cell number after ex vivo-expansion increased about 140-fold compared to that of freshly isolated PBMC within 2 weeks. Approximately 78% of the expanded and activated NKL using the house-developed protocol was NK cell and NKT cells even without a NK cell-sorting step. In addition, the expanded and activated NKL demonstrated potent cytotoxicity against liver cancer in vitro and in vivo. CONCLUSION: The house-developed method can be a new and effective strategy to prepare clinically applicable NKL for autologous NK cell-based anti-tumor immunotherapy. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12885-019-6034-1) contains supplementary material, which is available to authorized users.
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spelling pubmed-67008352019-08-26 Cytotoxic effects of ex vivo-expanded natural killer cell-enriched lymphocytes (MYJ1633) against liver cancer Choi, Jung-Won Lee, Eui Soo Kim, Se Young Park, Su Il Oh, Sena Kang, Jung Hwa Ryu, Hyun Aae Lee, Seahyoung BMC Cancer Research Article BACKGROUND: Adoptive transfer of immune cells such as T cells and natural killer (NK) cells has emerged as a targeted method of controlling the immune system against cancer. Despite their significant therapeutic potential, efficient methods to generate adequate numbers of NK cells are lacking and ex vivo-expansion and activation of NK cells is currently under intensive investigation. The primary purpose of this study was to develop an effective method for expansion and activation of the effector cells with high proportion of NK cells and increasing cytotoxicity against liver cancer in a short time period. METHODS: Expanded NK cell-enriched lymphocytes (NKL) designated as “MYJ1633” were prepared by using autologous human plasma, cytokines (IL-2, IL-12 and IL-18) and agonistic antibodies (CD16, CD56 and NKp46) without an NK cell-sorting step. The characteristics of NKL were compared to those of freshly isolated PBMCs. In addition, the cytotoxic effect of the NKL on liver cancer cell was examined in vitro and in vivo. RESULTS: The total cell number after ex vivo-expansion increased about 140-fold compared to that of freshly isolated PBMC within 2 weeks. Approximately 78% of the expanded and activated NKL using the house-developed protocol was NK cell and NKT cells even without a NK cell-sorting step. In addition, the expanded and activated NKL demonstrated potent cytotoxicity against liver cancer in vitro and in vivo. CONCLUSION: The house-developed method can be a new and effective strategy to prepare clinically applicable NKL for autologous NK cell-based anti-tumor immunotherapy. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12885-019-6034-1) contains supplementary material, which is available to authorized users. BioMed Central 2019-08-19 /pmc/articles/PMC6700835/ /pubmed/31426763 http://dx.doi.org/10.1186/s12885-019-6034-1 Text en © The Author(s). 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided 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 Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Choi, Jung-Won
Lee, Eui Soo
Kim, Se Young
Park, Su Il
Oh, Sena
Kang, Jung Hwa
Ryu, Hyun Aae
Lee, Seahyoung
Cytotoxic effects of ex vivo-expanded natural killer cell-enriched lymphocytes (MYJ1633) against liver cancer
title Cytotoxic effects of ex vivo-expanded natural killer cell-enriched lymphocytes (MYJ1633) against liver cancer
title_full Cytotoxic effects of ex vivo-expanded natural killer cell-enriched lymphocytes (MYJ1633) against liver cancer
title_fullStr Cytotoxic effects of ex vivo-expanded natural killer cell-enriched lymphocytes (MYJ1633) against liver cancer
title_full_unstemmed Cytotoxic effects of ex vivo-expanded natural killer cell-enriched lymphocytes (MYJ1633) against liver cancer
title_short Cytotoxic effects of ex vivo-expanded natural killer cell-enriched lymphocytes (MYJ1633) against liver cancer
title_sort cytotoxic effects of ex vivo-expanded natural killer cell-enriched lymphocytes (myj1633) against liver cancer
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6700835/
https://www.ncbi.nlm.nih.gov/pubmed/31426763
http://dx.doi.org/10.1186/s12885-019-6034-1
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