Cargando…
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...
Autores principales: | , , , , , , , , , , , |
---|---|
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 |
_version_ | 1782255637253586944 |
---|---|
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. |
format | Online Article Text |
id | pubmed-3543306 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT limokjae gmpcompliantlargescaleexpandedallogeneicnaturalkillercellshavepotentcytolyticactivityagainstcancercellsinvitroandinvivo AT leeyuna gmpcompliantlargescaleexpandedallogeneicnaturalkillercellshavepotentcytolyticactivityagainstcancercellsinvitroandinvivo AT chunghyejin gmpcompliantlargescaleexpandedallogeneicnaturalkillercellshavepotentcytolyticactivityagainstcancercellsinvitroandinvivo AT herjunghyun gmpcompliantlargescaleexpandedallogeneicnaturalkillercellshavepotentcytolyticactivityagainstcancercellsinvitroandinvivo AT kangsangmi gmpcompliantlargescaleexpandedallogeneicnaturalkillercellshavepotentcytolyticactivityagainstcancercellsinvitroandinvivo AT jungmiyoung gmpcompliantlargescaleexpandedallogeneicnaturalkillercellshavepotentcytolyticactivityagainstcancercellsinvitroandinvivo AT minbokyung gmpcompliantlargescaleexpandedallogeneicnaturalkillercellshavepotentcytolyticactivityagainstcancercellsinvitroandinvivo AT shinhyejin gmpcompliantlargescaleexpandedallogeneicnaturalkillercellshavepotentcytolyticactivityagainstcancercellsinvitroandinvivo AT kimtaemin gmpcompliantlargescaleexpandedallogeneicnaturalkillercellshavepotentcytolyticactivityagainstcancercellsinvitroandinvivo AT heodaeseog gmpcompliantlargescaleexpandedallogeneicnaturalkillercellshavepotentcytolyticactivityagainstcancercellsinvitroandinvivo AT hwangyukyeong gmpcompliantlargescaleexpandedallogeneicnaturalkillercellshavepotentcytolyticactivityagainstcancercellsinvitroandinvivo AT shineuicheol gmpcompliantlargescaleexpandedallogeneicnaturalkillercellshavepotentcytolyticactivityagainstcancercellsinvitroandinvivo |