Cytokine-induced killer cells in the treatment of patients with solid carcinomas: a systematic review and pooled analysis

Abstract

Background aims. The aim of this study was to evaluate the efficacy and safety of cytokine-induced killer (CIK) cell therapy for solid carcinomas. Methods. We performed a computerized search of phase II/III clinical trial databases of CIK cell-based therapy using a combination of the terms ‘cytokine-induced killer cells’, ‘tumor’ and ‘cancer’. Results. Treatment with CIK cells was associated with a significantly improved half-year survival (P = 0.003), 1-year survival (P = 0.0005), 2-year survival (P < 0.01) and mean survival time (MST) (P < 0.001). Patients in the CIK group showed a prolonged half-year progression-free survival (PFS) (P < 0.01), 1-year PFS (P < 0.01) and median time to progression (MTTP) (P < 0.001). A favored disease control rate (DCR) was observed in patients receiving CIK cell therapy, while the objective response rate (ORR) was not altered (P = 0.05) compared with the non-CIK group (P = 0.007). CIK cell therapy could also reduce the adverse effects of grade III and IV leukopenia caused by chemotherapy (P = 0.002) and diminish hepatitis B virus (HBV)-DNA content (P < 0.01). However, the incidence of fever in the CIK therapy group was significantly higher than in the non-CIK group (P = 0.02). The percentage of CD3⁺ , CD4⁺ , CD4⁺ CD8⁺ , CD3 – CD56⁺ and CD3⁺ CD56⁺ T-lymphocyte subsets in the peripheral blood of cancer patients was significantly increased, whereas the percentage of CD8⁺ T-lymphocyte cells was significantly decreased in the CIK group compared with the non-CIK group (P < 0.01). Conclusions. CIK cell therapy has demonstrated a significant superiority in prolonging the MST, PFS, DCR and quality of life (QoL) of patients.

Key words::

• cytokine-induced killer cells
• meta-analysis
• solid carcinomas

Acknowledgments

This study was supported by Shanghai Municipal Natural Science Foundation (project number 09ZR1417900), leading academic discipline project of Shanghai Municipal Education Committee (project number J50208), Shanghai Pujiang Program (project number 11PJ1406500) and the National Natural Science Funds (project number 81102015).

Conflict of interest: The authors have declared that no conflict of interest exists.

Author contributions: Lei Tang and Ying-Chun Xu performed the computerized search of the trials, contacted experts and participated in the trial selection. Yue Ma and Zan Zhang participated in the trial selection and performed the statistical analysis. Hong-Xia Wang conceived the study. All authors read and approved the final manuscript.