{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,7]],"date-time":"2025-11-07T09:22:14Z","timestamp":1762507334875,"version":"3.37.3"},"reference-count":19,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2018,3,14]],"date-time":"2018-03-14T00:00:00Z","timestamp":1520985600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002924","name":"Federaci\u00f3n Espa\u00f1ola de Enfermedades Raras","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002924","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Transfusion"],"published-print":{"date-parts":[[2018,6]]},"abstract":"<jats:sec><jats:title>BACKGROUND<\/jats:title><jats:p>Cancer immunotherapy involving natural killer (NK) cells has gained interest. Here we report two methods to obtain interleukin (IL)\u201015\u2013activated NK cells for clinical use.<\/jats:p><\/jats:sec><jats:sec><jats:title>STUDY DESIGN AND METHODS<\/jats:title><jats:p>IL\u201015\u2013activated NK cell products were obtained after 1) enrichment from healthy haploidentical donors' peripheral blood mononuclear cells (PBMNCs) collected by nonmobilized apheresis by a two\u2010step magnetic procedure, depletion of CD3+ cells followed by selection of CD56+ cells and ex vivo overnight stimulation with IL\u201015 (NKIL15); and 2) expansion using the K562\u2010mb15\u201041BBL cell line (NKAE), from autologous PBMNCs from patients with multiple myeloma or expansion from healthy haploidentical PBMNCs obtained from whole blood using the same previous cell line. We analyzed the NK cell recovery and expansion, T\u00a0cell depletion, phenotype, cytotoxicity, safety, and genomic stability of two good manufacturing practices (GMP)\u2013grade IL\u201015\u2013activated NK cell products.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>The number of NK cells obtained from NKIL15 cell and NKAE cell products was similar; however, there were significantly fewer T cells in the NKIL15 cell product. The haploidentical NKAE cell product contained more T cells than the autologous NKAE cell product. The surface expression of the activating receptors CD69, CD25, natural killer group\u20102 member D receptor, NKp44, NKp46, NKp30, and DNA accessory molecule 1 was up\u00a0regulated in both NK cell products. NKIL15 cell and NKAE cell products had significantly higher lytic activity than unstimulated NK cells and showed no lytic activity against PBMNCs from healthy donors. No genetic alterations or potential oncogenic effects were found.<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSION<\/jats:title><jats:p>Different GMP\u2010grade procedures can be used to obtain large numbers of highly IL\u201015\u2013activated NK cells with extremely low T\u00a0cell content for clinical use.<\/jats:p><\/jats:sec>","DOI":"10.1111\/trf.14573","type":"journal-article","created":{"date-parts":[[2018,3,15]],"date-time":"2018-03-15T12:29:04Z","timestamp":1521116944000},"page":"1340-1347","source":"Crossref","is-referenced-by-count":13,"title":["How do we manufacture clinical\u2010grade interleukin\u201015\u2013stimulated natural killer cell products for cancer treatment?"],"prefix":"10.1111","volume":"58","author":[{"given":"Luc\u00eda","family":"Fern\u00e1ndez","sequence":"first","affiliation":[{"name":"Clinical Research Department Spanish National Cancer Research Center, CNIO"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alejandra","family":"Leivas","sequence":"additional","affiliation":[{"name":"Hematology Department University Hospital 12 de Octubre"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jaime","family":"Valent\u00edn","sequence":"additional","affiliation":[{"name":"Tumor Immunology Lab, IdiPAZ"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adela","family":"Escudero","sequence":"additional","affiliation":[{"name":"Medical and Molecular Genetics Institute, INGEMM"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dolores","family":"Corral","sequence":"additional","affiliation":[{"name":"Pediatric Department Autonomous University of Madrid"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raquel","family":"de Paz","sequence":"additional","affiliation":[{"name":"Hematology Department"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"Vela","sequence":"additional","affiliation":[{"name":"Tumor Immunology Lab, IdiPAZ"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Bueno","sequence":"additional","affiliation":[{"name":"Pediatric Hemato\u2010Oncology"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rebeca","family":"Rodr\u00edguez","sequence":"additional","affiliation":[{"name":"Immunology Department"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juan Manuel","family":"Torres","sequence":"additional","affiliation":[{"name":"Immunology Department"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mariana","family":"D\u00edaz\u2010Almir\u00f3n","sequence":"additional","affiliation":[{"name":"Biostatistics Department La Paz University Hospital Madrid Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eduardo","family":"L\u00f3pez\u2010Collazo","sequence":"additional","affiliation":[{"name":"Tumor Immunology Lab, IdiPAZ"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7908-0063","authenticated-orcid":false,"given":"Joaquin","family":"Martinez\u2010Lopez","sequence":"additional","affiliation":[{"name":"Hematology Department University Hospital 12 de Octubre"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonio","family":"P\u00e9rez\u2010Mart\u00ednez","sequence":"additional","affiliation":[{"name":"Pediatric Hemato\u2010Oncology"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2018,3,14]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.2217\/imt.11.131"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1005641107"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcmd.2004.08.013"},{"key":"e_1_2_8_5_1","first-page":"884","article-title":"Interleukin\u201018 (IL\u201018) synergizes with IL\u20102 to enhance cytotoxicity, interferon\u2010gamma production, and expansion of natural killer cells","volume":"61","author":"Son YI","year":"2001","journal-title":"Cancer Res"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcyt.2015.07.011"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/cei.12034"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-08-3712"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2013.00118"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12185-007-0018-7"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/0022-1759(96)00063-4"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1080\/2162402X.2016.1250051"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a014373"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1206063"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2014-07-592881"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2012.09.009"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0030264"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4939-3684-7_15"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-10-0735"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2015.07.042"}],"container-title":["Transfusion"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Ftrf.14573","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/trf.14573","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/trf.14573","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/trf.14573","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,28]],"date-time":"2023-08-28T11:26:31Z","timestamp":1693221991000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/trf.14573"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,3,14]]},"references-count":19,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2018,6]]}},"alternative-id":["10.1111\/trf.14573"],"URL":"https:\/\/doi.org\/10.1111\/trf.14573","archive":["Portico"],"relation":{},"ISSN":["0041-1132","1537-2995"],"issn-type":[{"type":"print","value":"0041-1132"},{"type":"electronic","value":"1537-2995"}],"subject":[],"published":{"date-parts":[[2018,3,14]]}}}