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Many studies have focused on the therapeutic effects, but the methods of activating and culturing T\/NK cells without excessive exhaustion during the initial stages of the production of CB\u2010derived CAR\u2010T\/NK cells are yet to be established. The activation and culture conditions developed for peripheral blood (PB) CAR\u2010T\/NK cells have been used for CB\u2010CAR\u2010T\/NK cells, but there are differences in the composition and maturity of PB and CB lymphocytes. Thus, this study aims to optimize activation and culture conditions for the production of CB\u2010CAR\u2010T\/NK cells. We compared different doses of various cytokines and found that the balance between activation and exhaustion was best with stimulation with a CD3\/CD28 agonist followed by 40\u2009U\/mL interleukin (IL)\u20107+ 40\u2009U\/mL IL\u201015 for PB\u2010T cells; 40\u2009U\/mL IL\u20102+ 40\u2009U\/mL IL\u20107+ 40\u2009U\/mL IL\u201015 for CB\u2010T cells; 40\u2009U\/mL IL\u20102+ 40\u2009U\/mL IL\u201015 for PB\u2010NK cells; and 40\u2009U\/mL IL\u20102+ 200\u2009U\/mL IL\u201015 for CB\u2010NK cells. Using killing assays, we confirmed that these cytokine protocols improved the anti\u2010tumour effects. These results will be useful for the development of CB\u2010CAR\u2010T\/NK\u2010cell therapies and suggest the potential of these modalities.<\/jats:p>","DOI":"10.1111\/bjh.70139","type":"journal-article","created":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T06:42:43Z","timestamp":1759300963000},"page":"1863-1873","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Optimizing activation and culture conditions for the production of\u00a0cord blood\u2010derived\n                    <scp>CAR<\/scp>\n                    \u2010T and natural killer cells"],"prefix":"10.1111","volume":"207","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4336-1952","authenticated-orcid":false,"given":"Naokazu","family":"Nakamura","sequence":"first","affiliation":[{"name":"Division of Molecular and Medical Genetics, Center for Gene &amp; Cell Therapy The Institute of Medical Science, The University of Tokyo  Tokyo 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