Frontiers in neurology · 2026
Cytokine-induced killer cells combined with temozolomide suppress glioblastoma progression in an orthotopic model and demonstrate clinical feasibility in recurrent glioblastoma.
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Park Young Kyu, Yang Dong Won, Park Kyun Woo, Nam Gun He, Lee Choon-Soo, Kim Tae Whan, Kim Jong-Yeup, Choi Jong Gwon
Аннотация
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.
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.