Please use this identifier to cite or link to this item:
https://doi.org/10.1186/1756-9966-29-134
DC Field | Value | |
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dc.title | Ex-vivo expanded human NK cells express activating receptors that mediate cytotoxicity of allogeneic and autologous cancer cell lines by direct recognition and antibody directed cellular cytotoxicity | |
dc.contributor.author | Voskens, C.J | |
dc.contributor.author | Watanabe, R | |
dc.contributor.author | Rollins, S | |
dc.contributor.author | Campana, D | |
dc.contributor.author | Hasumi, K | |
dc.contributor.author | Mann, D.L | |
dc.date.accessioned | 2020-10-20T08:18:36Z | |
dc.date.available | 2020-10-20T08:18:36Z | |
dc.date.issued | 2010 | |
dc.identifier.citation | Voskens, C.J, Watanabe, R, Rollins, S, Campana, D, Hasumi, K, Mann, D.L (2010). Ex-vivo expanded human NK cells express activating receptors that mediate cytotoxicity of allogeneic and autologous cancer cell lines by direct recognition and antibody directed cellular cytotoxicity. Journal of Experimental and Clinical Cancer Research 29 (1) : 134. ScholarBank@NUS Repository. https://doi.org/10.1186/1756-9966-29-134 | |
dc.identifier.issn | 1756-9966 | |
dc.identifier.uri | https://scholarbank.nus.edu.sg/handle/10635/178196 | |
dc.description.abstract | Background: The possibility that autologous NK cells could serve as an effective treatment modality for solid tumors has long been considered. However, implementation is hampered by (i) the small number of NK cells in peripheral blood, (ii) the difficulties associated with large-scale production of GMP compliant cytolytic NK cells, (iii) the need to activate the NK cells in order to induce NK cell mediated killing and (iv) the constraints imposed by autologous inhibitory receptor-ligand interactions. To address these issues, we determined (i) if large numbers of NK cells could be expanded from PBMC and GMP compliant cell fractions derived by elutriation, (ii) their ability to kill allogeneic and autologous tumor targets by direct cytotoxitiy and by antibody-mediated cellular cytotoxicity and (iii) defined NK cell specific receptor-ligand interactions that mediate tumor target cell killing. Methods: Human NK cells were expanded during 14 days. Expansion efficiency, NK receptor repertoire before and after expansion, expression of NK specific ligands, cytolytic activity against allogeneic and autologous tumor targets, with and without the addition of chimeric EGFR monoclonal antibody, were investigated. Results: Cell expansion shifted the NK cell receptor repertoire towards activation and resulted in cytotoxicity against various allogeneic tumor cell lines and autologous gastric cancer cells, while sparing normal PBMC. Blocking studies confirmed that autologous cytotoxicity is established through multiple activating receptor-ligand interactions. Importantly, expanded NK cells also mediated ADCC in an autologous and allogeneic setting by antibodies that are currently being used to treat patients with select solid tumors. Conclusion: These data demonstrate that large numbers of cytolytic NK cells can be generated from PBMC and lymphocyte-enriched fractions obtained by GMP compliant counter current elutriation from PBMC, establishing the preclinical evidence necessary to support clinical trials utilizing autologous expanded NK cells, both directly and in combination with monoclonal antibodies in future cell-based immunotherapy in select solid tumors. © 2010 Voskens et al; licensee BioMed Central Ltd. | |
dc.publisher | BMC | |
dc.rights | Attribution 4.0 International | |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | |
dc.source | Unpaywall 20201031 | |
dc.subject | natural killer cell receptor | |
dc.subject | EGFR protein, human | |
dc.subject | epidermal growth factor receptor | |
dc.subject | immunoglobulin receptor | |
dc.subject | ligand | |
dc.subject | monoclonal antibody | |
dc.subject | allogeneic cancer cell | |
dc.subject | article | |
dc.subject | autologous cancer cell | |
dc.subject | cancer cell | |
dc.subject | cancer cell culture | |
dc.subject | cell expansion | |
dc.subject | cytotoxicity | |
dc.subject | ex vivo study | |
dc.subject | human | |
dc.subject | human cell | |
dc.subject | lymphocyte | |
dc.subject | natural killer cell | |
dc.subject | peripheral blood mononuclear cell | |
dc.subject | priority journal | |
dc.subject | protein expression | |
dc.subject | stomach cancer | |
dc.subject | antibody dependent cellular cytotoxicity | |
dc.subject | cell proliferation | |
dc.subject | cell separation | |
dc.subject | coculture | |
dc.subject | immunology | |
dc.subject | immunophenotyping | |
dc.subject | lymphocyte activation | |
dc.subject | phenotype | |
dc.subject | stomach tumor | |
dc.subject | time | |
dc.subject | tumor cell line | |
dc.subject | Antibodies, Monoclonal | |
dc.subject | Antibody-Dependent Cell Cytotoxicity | |
dc.subject | Cell Line, Tumor | |
dc.subject | Cell Proliferation | |
dc.subject | Cell Separation | |
dc.subject | Coculture Techniques | |
dc.subject | Humans | |
dc.subject | Immunophenotyping | |
dc.subject | Killer Cells, Natural | |
dc.subject | Ligands | |
dc.subject | Lymphocyte Activation | |
dc.subject | Phenotype | |
dc.subject | Receptor, Epidermal Growth Factor | |
dc.subject | Receptors, Immunologic | |
dc.subject | Stomach Neoplasms | |
dc.subject | Time Factors | |
dc.type | Article | |
dc.contributor.department | PAEDIATRICS | |
dc.description.doi | 10.1186/1756-9966-29-134 | |
dc.description.sourcetitle | Journal of Experimental and Clinical Cancer Research | |
dc.description.volume | 29 | |
dc.description.issue | 1 | |
dc.description.page | 134 | |
dc.published.state | published | |
Appears in Collections: | Staff Publications Elements |
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