A clinical study of cytokine-induced killer cells for the treatment of refractory lymphoma

Abstract

Cytokine-induced killer (CIK) cell therapy, an adoptive T-cell immunotherapy, has been reported to be a safe and effective mode of treatment for patients with metastatic diseases, lymphoma and acute leukaemia. To investigate the clinical efficacy of cytokine-induced killer cells for the treatment of refractory lymphoma, the present clinical study was conducted. A total of 8 male patients with a mean age of 41 years (range 22-65) who were pathologically diagnosed with malignant lymphoma (Hodgkin's disease, 2 and non-Hodgkin's lymphoma, 6) were enrolled. CIK cells were expanded by priming with IFN-γ, monoclonal antibody (mAb) to CD3 and IL-1α, followed by the addition of IL-2 the following day using peripheral blood mononuclear cells (PBMCs) of the 8 male patients. The CIK cells were then transfused back to the patients as treatment. On day 13, the CIK cell count reached 7-18×1019 (mean, 12.7×109), a 44- to 140-fold increase (mean, 98-fold). The average percentage of cells expressing CD3+, CD4+, CD8+ and CD3+CD56+ were also increased from 50.9±3.5, 29.9±1.7, 41.3±3.2, 1.6±0.2% to 90.2±1.6, 40.6±5.5, 52.8±4.9 and 33.1±4.0%, respectively. Patients showed measurable radiographic tumor reduction, increased T-cell subset levels, and relief of symptoms after treatment. No severe toxicity or side effects were reported. CIK cells developed by this culture method have a high in vitro proliferation rate and tumor-killing capacity. In conclusion, CIK cell treatment of patients with malignant lymphoma achieves effective clinical responses, causing few side effects.