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Peer-reviewedCC BYFrontiers in neurology

Cytokine-induced killer cells combined with temozolomide suppress glioblastoma progression in an orthotopic model and demonstrate clinical feasibility in recurrent glioblastoma

  • Young Kyu Park1
  • Dong Won Yang2
  • Kyun Woo Park3
  • Gun He Nam4
  • Choon-Soo Lee4
  • Tae Whan Kim5
  • Jong-Yeup Kim2
  • Jong Gwon Choi1
5 affiliations
  1. 1Department of Oncology-Hematology, Konyang University Hospital , ,
  2. 2Department of Biomedical Informatics, College of Medicine, Konyang University , ,
  3. 3Department of Medical Oncology, Yuseong Sun General Hospital , ,
  4. 4Product Development Division, GC Cell Corp. , ,
  5. 5R&D M Unit, GC Cell Corp. , ,
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Abstract

Introduction: 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.

Methods: 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.

Results: 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 ( p = 0.0054). 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 ( p = 0.0663). Quantitative H&E analysis showed an overall group difference in tumor area fraction ( p = 0.0376), 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.

Discussion: 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.

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Cite

BibTeXRIS
BibTeX
@article{park2026cytokineinduced,
  title = {{Cytokine-induced killer cells combined with temozolomide suppress glioblastoma progression in an orthotopic model and demonstrate clinical feasibility in recurrent glioblastoma}},
  author = {Young Kyu Park and Dong Won Yang and Kyun Woo Park and Gun He Nam and Choon-Soo Lee and Tae Whan Kim and Jong-Yeup Kim and Jong Gwon Choi},
  journal = {Frontiers in neurology},
  year = {2026},
  month = sep,
  doi = {10.3389/fneur.2026.1895857},
  url = {https://europepmc.org/article/PMC/PMC13662175},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Cytokine-induced killer cells combined with temozolomide suppress glioblastoma progression in an orthotopic model and demonstrate clinical feasibility in recurrent glioblastoma
AU  - Young Kyu Park
AU  - Dong Won Yang
AU  - Kyun Woo Park
AU  - Gun He Nam
AU  - Choon-Soo Lee
AU  - Tae Whan Kim
AU  - Jong-Yeup Kim
AU  - Jong Gwon Choi
PY  - 2026
DA  - 2026/09/30
JO  - Frontiers in neurology
DO  - 10.3389/fneur.2026.1895857
UR  - https://europepmc.org/article/PMC/PMC13662175
AB  - Introduction: 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.  Methods: 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.  Results: 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 ( p = 0.0054). 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 ( p = 0.0663). Quantitative H&E analysis showed an overall group difference in tumor area fraction ( p = 0.0376), 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.  Discussion: 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.
SN  - 1664-2295
ER  -