{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T06:56:21Z","timestamp":1790751381299,"version":"4.1.0"},"reference-count":30,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:00:00Z","timestamp":1790726400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"GC Cell, Republic of Korea"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Glioblastoma (GBM) remains an aggressive primary brain tumor with limited therapeutic options after recurrence. Cytokine-induced killer (CIK) cells are ex vivo-expanded cytotoxic lymphocytes with T-cell and natural killer-like properties. We evaluated CIK-cell-based therapy using an orthotopic LN229-luciferase GBM model and a retrospective cohort of patients with recurrent GBM.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Twelve independently manufactured patient-derived CIK-cell products were phenotypically characterized. In the orthotopic model, control, temozolomide (TMZ), and TMZ+CIK groups (n = 4 per group) were monitored by longitudinal bioluminescence imaging, with quantitative histological and immunohistochemical analyses. Clinical outcomes and safety were retrospectively evaluated in 12 heavily pretreated patients with recurrent GBM.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Expanded CIK-cell products showed a predominant effector-memory phenotype and high NKG2D and DNAM-1 expression. Longitudinal bioluminescence imaging demonstrated a significant treatment-by-time interaction among the three groups through Week 4 (\n                      <jats:italic>p<\/jats:italic>\n                      \u202f=\u202f0.0054). At Week 4, both TMZ and TMZ+CIK showed significantly lower radiance than control, whereas TMZ and TMZ+CIK did not differ significantly. An exploratory comparison between TMZ and TMZ+CIK through Week 8 was not significant (\n                      <jats:italic>p<\/jats:italic>\n                      \u202f=\u202f0.0663). Quantitative H&amp;amp;E analysis showed an overall group difference in tumor area fraction (\n                      <jats:italic>p<\/jats:italic>\n                      \u202f=\u202f0.0376), whereas Granzyme B and CD56 staining did not differ significantly. In the clinical cohort, stable disease was the best recorded response in all evaluable patients; median progression-free survival was 10.5 months and median overall survival was 14.2 months. CIK-cell-based therapy was generally well tolerated.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>These findings provide quantitative preclinical evidence of treatment-associated antitumor activity and support the clinical feasibility of CIK-cell-based therapy in recurrent GBM. However, the study does not establish a statistically significant incremental preclinical benefit of adding CIK cells to TMZ or clinical therapeutic efficacy. Prospective, adequately powered controlled studies are warranted.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fneur.2026.1895857","type":"journal-article","created":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T06:01:45Z","timestamp":1790748105000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Cytokine-induced killer cells combined with temozolomide suppress glioblastoma progression in an orthotopic model and demonstrate clinical feasibility in recurrent glioblastoma"],"prefix":"10.3389","volume":"17","author":[{"given":"Young Kyu","family":"Park","sequence":"first","affiliation":[{"name":"Department of Oncology-Hematology, Konyang University Hospital","place":["Daejeon, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong Won","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Biomedical Informatics, College of Medicine, Konyang University","place":["Daejeon, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyun Woo","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Yuseong Sun General Hospital","place":["Daejeon, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gun He","family":"Nam","sequence":"additional","affiliation":[{"name":"Product Development Division, GC Cell Corp.","place":["Yongin-si, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Choon-Soo","family":"Lee","sequence":"additional","affiliation":[{"name":"Product Development Division, GC Cell Corp.","place":["Yongin-si, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tae Whan","family":"Kim","sequence":"additional","affiliation":[{"name":"R&D M Unit, GC Cell Corp.","place":["Yongin-si, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jong-Yeup","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Biomedical Informatics, College of Medicine, Konyang University","place":["Daejeon, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jong Gwon","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Oncology-Hematology, Konyang University Hospital","place":["Daejeon, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,30]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"180","DOI":"10.1200\/OP.22.00476","article-title":"Key clinical principles in the management of glioblastoma","volume":"19","author":"Kotecha","year":"2023","journal-title":"JCO Oncol 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