Antigen Presenting Cell-Mediated Expansion of Human Umbilical Cord Blood Yields Log-Scale Expansion of Natural Killer Cells with Anti-Myeloma Activity
Natural killer (NK) cells are important mediators of anti-tumor immunity and are active against several hematologic malignancies, including multiple myeloma (MM). Umbilical cord blood (CB) is a promising source of allogeneic NK cells but large scale ex vivo expansion is required for generation of cl...
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| Format: | Online |
| Language: | English |
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Public Library of Science
2013
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| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3800010/ |
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pubmed-3800010 |
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pubmed-38000102013-11-07 Antigen Presenting Cell-Mediated Expansion of Human Umbilical Cord Blood Yields Log-Scale Expansion of Natural Killer Cells with Anti-Myeloma Activity Shah, Nina Martin-Antonio, Beatriz Yang, Hong Ku, Stephanie Lee, Dean A. Cooper, Laurence J. N. Decker, William K. Li, Sufang Robinson, Simon N. Sekine, Takuya Parmar, Simrit Gribben, John Wang, Michael Rezvani, Katy Yvon, Eric Najjar, Amer Burks, Jared Kaur, Indreshpal Champlin, Richard E. Bollard, Catherine M. Shpall, Elizabeth J. Research Article Natural killer (NK) cells are important mediators of anti-tumor immunity and are active against several hematologic malignancies, including multiple myeloma (MM). Umbilical cord blood (CB) is a promising source of allogeneic NK cells but large scale ex vivo expansion is required for generation of clinically relevant CB-derived NK (CB-NK) cell doses. Here we describe a novel strategy for expanding NK cells from cryopreserved CB units using artificial antigen presenting feeder cells (aAPC) in a gas permeable culture system. After 14 days, mean fold expansion of CB-NK cells was 1848-fold from fresh and 2389-fold from cryopreserved CB with >95% purity for NK cells (CD56+/CD3−) and less than 1% CD3+ cells. Though surface expression of some cytotoxicity receptors was decreased, aAPC-expanded CB-NK cells exhibited a phenotype similar to CB-NK cells expanded with IL-2 alone with respect to various inhibitory receptors, NKG2C and CD94 and maintained strong expression of transcription factors Eomesodermin and T-bet. Furthermore, CB-NK cells formed functional immune synapses with and demonstrated cytotoxicity against various MM targets. Finally, aAPC-expanded CB-NK cells showed significant in vivo activity against MM in a xenogenic mouse model. Our findings introduce a clinically applicable strategy for the generation of highly functional CB-NK cells which can be used to eradicate MM. Public Library of Science 2013-10-18 /pmc/articles/PMC3800010/ /pubmed/24204673 http://dx.doi.org/10.1371/journal.pone.0076781 Text en © 2013 Shah 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. |
| repository_type |
Open Access Journal |
| institution_category |
Foreign Institution |
| institution |
US National Center for Biotechnology Information |
| building |
NCBI PubMed |
| collection |
Online Access |
| language |
English |
| format |
Online |
| author |
Shah, Nina Martin-Antonio, Beatriz Yang, Hong Ku, Stephanie Lee, Dean A. Cooper, Laurence J. N. Decker, William K. Li, Sufang Robinson, Simon N. Sekine, Takuya Parmar, Simrit Gribben, John Wang, Michael Rezvani, Katy Yvon, Eric Najjar, Amer Burks, Jared Kaur, Indreshpal Champlin, Richard E. Bollard, Catherine M. Shpall, Elizabeth J. |
| spellingShingle |
Shah, Nina Martin-Antonio, Beatriz Yang, Hong Ku, Stephanie Lee, Dean A. Cooper, Laurence J. N. Decker, William K. Li, Sufang Robinson, Simon N. Sekine, Takuya Parmar, Simrit Gribben, John Wang, Michael Rezvani, Katy Yvon, Eric Najjar, Amer Burks, Jared Kaur, Indreshpal Champlin, Richard E. Bollard, Catherine M. Shpall, Elizabeth J. Antigen Presenting Cell-Mediated Expansion of Human Umbilical Cord Blood Yields Log-Scale Expansion of Natural Killer Cells with Anti-Myeloma Activity |
| author_facet |
Shah, Nina Martin-Antonio, Beatriz Yang, Hong Ku, Stephanie Lee, Dean A. Cooper, Laurence J. N. Decker, William K. Li, Sufang Robinson, Simon N. Sekine, Takuya Parmar, Simrit Gribben, John Wang, Michael Rezvani, Katy Yvon, Eric Najjar, Amer Burks, Jared Kaur, Indreshpal Champlin, Richard E. Bollard, Catherine M. Shpall, Elizabeth J. |
| author_sort |
Shah, Nina |
| title |
Antigen Presenting Cell-Mediated Expansion of Human Umbilical Cord Blood Yields Log-Scale Expansion of Natural Killer Cells with Anti-Myeloma Activity |
| title_short |
Antigen Presenting Cell-Mediated Expansion of Human Umbilical Cord Blood Yields Log-Scale Expansion of Natural Killer Cells with Anti-Myeloma Activity |
| title_full |
Antigen Presenting Cell-Mediated Expansion of Human Umbilical Cord Blood Yields Log-Scale Expansion of Natural Killer Cells with Anti-Myeloma Activity |
| title_fullStr |
Antigen Presenting Cell-Mediated Expansion of Human Umbilical Cord Blood Yields Log-Scale Expansion of Natural Killer Cells with Anti-Myeloma Activity |
| title_full_unstemmed |
Antigen Presenting Cell-Mediated Expansion of Human Umbilical Cord Blood Yields Log-Scale Expansion of Natural Killer Cells with Anti-Myeloma Activity |
| title_sort |
antigen presenting cell-mediated expansion of human umbilical cord blood yields log-scale expansion of natural killer cells with anti-myeloma activity |
| description |
Natural killer (NK) cells are important mediators of anti-tumor immunity and are active against several hematologic malignancies, including multiple myeloma (MM). Umbilical cord blood (CB) is a promising source of allogeneic NK cells but large scale ex vivo expansion is required for generation of clinically relevant CB-derived NK (CB-NK) cell doses. Here we describe a novel strategy for expanding NK cells from cryopreserved CB units using artificial antigen presenting feeder cells (aAPC) in a gas permeable culture system. After 14 days, mean fold expansion of CB-NK cells was 1848-fold from fresh and 2389-fold from cryopreserved CB with >95% purity for NK cells (CD56+/CD3−) and less than 1% CD3+ cells. Though surface expression of some cytotoxicity receptors was decreased, aAPC-expanded CB-NK cells exhibited a phenotype similar to CB-NK cells expanded with IL-2 alone with respect to various inhibitory receptors, NKG2C and CD94 and maintained strong expression of transcription factors Eomesodermin and T-bet. Furthermore, CB-NK cells formed functional immune synapses with and demonstrated cytotoxicity against various MM targets. Finally, aAPC-expanded CB-NK cells showed significant in vivo activity against MM in a xenogenic mouse model. Our findings introduce a clinically applicable strategy for the generation of highly functional CB-NK cells which can be used to eradicate MM. |
| publisher |
Public Library of Science |
| publishDate |
2013 |
| url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3800010/ |
| _version_ |
1612019244929646592 |