Dendritic cells in combination with cytokine-induced killer cells in the treatment of stage Ⅱ-Ⅳ esophageal cancer
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Abstract:
Objective: To evaluate the safety and clinical efficacy of dendritic cells (DCs) combined with cytokine-induced killer (CIK) cells in the treatment of esophagus cancer and its effect on the lymphocyte subsets of peripheral blood mononuclear cells (PBMCs). Methods: PBMCs were collected from 20 patients with stage Ⅱ-Ⅳ esophagus cancer who were admitted to the Academy of Military Medical Sciences-Affiliated Hospital in Beijing between May 2011 and May 2013. Non-adherent PBMCs were induced to develop into CIK cells by IFN-γ, IL-2 500 U/ml and Anti-CD3 and adherent PBMCs were induced to develop into DCs by TNF-α, followed by transfection with surviving and muc-1 . On days 7, 9, 11, and 13, respectively, after PBMCs collection, DCs (3-10)×107 in 1 ml PBS) were given subcutaneously and days 11 and 13 CIK cells (2-15)×109 in 100 ml PBS. This treatment regimen was repeated at an interval of 3 months until substantial remission was achieved. Clinical outcomes and adverse effects were recorded during the treatment period. One week before treatment and one month after each treatment cycle, peripheral blood was collected and lymphocyte subsets were analyzed by flow cytometry. Results: Complete remission occurred in one case and partial remission in 6 cases while the disease remained at a stable state in 6 cases and at a progressive state in 7 cases after treatment. The overall response rate was 35% and the disease control rate was 65%. Treatment with CIKs and DCs significantly increased the percentage of both Th1 (\[14.5±13.3\]% vs \[3.6±5.9\]% and Th2 (\[1.0±0.7\]% vs \[0.6±0.5\]% as compared with the vehicle control ( P <0.05). No evident adverse events were observed. Conclusion: Infusion of DCs and CIK cells may improve the immunosuppression status and enhance the anti-tumor immunity in patients with stage Ⅱ-Ⅳ esophagus cancer, thereby having potential clinical implications.
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Project supported by the Major Science and Technology Foundation of “Twelve Five-year Plan” of China (No.2009zx09503)