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

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 ( 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.