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Expansion of human NK cells using K562 cells expressing OX40 ligand and short exposure to IL-21
DC Field | Value | Language |
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dc.contributor.author | Kweonl, SoonHo | - |
dc.contributor.author | Phan, Minh-Trang Thi | - |
dc.contributor.author | Chun, Sejong | - |
dc.contributor.author | Yu, HongBi | - |
dc.contributor.author | Kim, Jinho | - |
dc.contributor.author | Kim, Seokho | - |
dc.contributor.author | Lee, Jaemin | - |
dc.contributor.author | Ali, Alaa Kassim | - |
dc.contributor.author | Lee, Seung-Hwan | - |
dc.contributor.author | Kim, Sang-Ki | - |
dc.contributor.author | Doh, Junsang | - |
dc.contributor.author | Cho, Duck | - |
dc.date.accessioned | 2022-06-24T07:15:17Z | - |
dc.date.available | 2022-06-24T07:15:17Z | - |
dc.date.created | 2020-03-25 | - |
dc.date.created | 2020-03-25 | - |
dc.date.created | 2020-03-25 | - |
dc.date.issued | 2019-04 | - |
dc.identifier.citation | Frontiers in Immunology, Vol.10 No.APR, p. 879 | - |
dc.identifier.issn | 1664-3224 | - |
dc.identifier.uri | https://hdl.handle.net/10371/184025 | - |
dc.description.abstract | Background: Natural Killer (NK) cell-based immunotherapy used to treat cancer requires the adoptive transfer of a large number of activated NK cells. Here, we report a new effective method to expand human NK cells ex vivo using K562 cells genetically engineered (GE) to express OX40 ligand (K562-OX40L) in combination with a short exposure to soluble IL-21. In addition, we describe a possible mechanism of the NK cell expansion through the OX40 receptor-OX40 ligand axis which is dependent on NK cell homotypic interaction. Methods: K562-OX40L cells were generated by lentiviral transduction and were used as feeder cells to expand and activate NK cells from PBMCs in the presence of IL-2/IL-15. Soluble IL-21 was also added in various concentrations only once at the beginning of the culture. NK cells were expanded for 4-5 weeks, and the purity, expansion rate, phenotype and function (cytotoxicity, antibody-dependent cell-mediated cytotoxicity (ADCC), cytokine production, CD107a degranulation) of these expanded NK cells were compared to those generated by using K562 feeder cells. Results: The culture of NK cells with K562-OX40L cells in combination with the transient exposure to IL-21 highly enhanced NK cell expansion to approximately 2,000-fold after 4 weeks of culture, compared to a 303-fold expansion using the conventional K562 cells. Mechanistically, the OX40-OX40L axis between the feeder cells and NK cells as well as the homotypic interaction between NK cells through the OX40-OX40L axis were both necessary for NK cell expansion. The short exposure of NK cells to IL-21 had a synergistic effect with OX40 signaling for NK cell expansion. Apart from their enhanced expansion, NK cells grown with K562-OX40L feeder cells were similar to those grown with conventional K562 cells in regard to the surface expression of various receptors, cytotoxicity, ADCC, cytokine secretion, and CD107 degranulation. Conclusion: Our data suggest that OX40 ligand is a potent co-stimulant for the robust expansion of human NK cells and the homotypic NK cell interactions through the OX40-OX40L axis is a mechanism of NK cell expansion. | - |
dc.language | 영어 | - |
dc.publisher | Frontiers Media S.A. | - |
dc.title | Expansion of human NK cells using K562 cells expressing OX40 ligand and short exposure to IL-21 | - |
dc.type | Article | - |
dc.identifier.doi | 10.3389/fimmu.2019.00879 | - |
dc.citation.journaltitle | Frontiers in Immunology | - |
dc.identifier.wosid | 000465396200002 | - |
dc.identifier.scopusid | 2-s2.0-85066944479 | - |
dc.citation.number | APR | - |
dc.citation.startpage | 879 | - |
dc.citation.volume | 10 | - |
dc.description.isOpenAccess | Y | - |
dc.contributor.affiliatedAuthor | Doh, Junsang | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.subject.keywordPlus | NATURAL-KILLER-CELLS | - |
dc.subject.keywordPlus | T-CELLS | - |
dc.subject.keywordPlus | EX-VIVO | - |
dc.subject.keywordPlus | ACTIVATION | - |
dc.subject.keywordPlus | CD4 | - |
dc.subject.keywordAuthor | natural killer cells | - |
dc.subject.keywordAuthor | expansion | - |
dc.subject.keywordAuthor | IL-21 | - |
dc.subject.keywordAuthor | K562 | - |
dc.subject.keywordAuthor | OX40 ligand | - |
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