Curative effect of autologous dendritic cell stimulated by cytokine-induced killer cells on metastatic renal carcinoma
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Abstract:
Objective : To investigate the clinical effect and safety of autologous dendritic cells (DCs) stimulated by cytokine-induced killer (CIK) cells in patients with advanced renal cell carcinoma (RCC). Methods: During July 2011 to June 2012, peripheral blood mononuclear cells (PBMCs) were collected from 22 patients (12 males and 10 females, median age 60.8 years \[21-79 years\]) with advanced renal carcinoma in the Department of Medical Oncology of Suzhou Hospital affiliated to Nanjing Medical University, and DC-CIK cells were individually prepared from these PBMCs. Flow cytometry was performed to analyz the proportion of CD3+T, CD8+T, CD4+T, NK(CD3-CD56+)and NKT(CD3+CD56+)cells in the DC-CIK cells. The cytotoxicity of DC-CIK cells on leukemia K562 cells (sensitive to NK cells) and renal carcinoma 786-0 cells (insensitive to NK cells) was detected by MTT assay. DC-CIK cells therapy was started when the conventional therapy (surgery+chemotherapy+radiotherapy/ cytokine therapy) finished and continued for 4 weeks. Each time, about (5.0±0.5)×108 DC-CIK cells were returned through intravenous transfusion, and each patient received 5 times (one cycle) of DC-CIK cells intravenous infusion. The immunological index such as lymphocyte subsets and cytokine concentration in the peripheral blood were detected before and after DC-CIK infusion. The adverse reactions during the treatment were closely observed and recorded. Results: In the total number of DC-CIK cells, the proportion of CD3 positive (CD3+) lymphocytes was (86.92±5.32)%, while the proportions of CD3+CD56+NKT cells and CD3-CD56+ NK cells were (52.04±7.33)% and(7.85±3.15)% respectively. DC-CIK cells showed similar in vitro killing activities on 786-0 cells and K562 cells in vitro, with a killing rate of (16.5±1.7) % and (18.4±1.9) % respectively (P=0.014), when the ratio of effect cells and target cells was 3 ∶1. After patients received DC-CIK cell therapy, the proportion of peripheral lymphocyte sub-group (CD3+T, CD4+T, CD8+T and CD3-CD56+NK cells) showed no significant change (P>0.05); compared to the cytokine levels prior to DC-CIK cells infusion, the levels of interleukine 2 (IL-2), interleukin 12 (IL-12) and interferon gamma (IFN-r) increased significantly (P<0.05), while the levels of tumor necrosis factor-α (TNF-α) and interleukine 10 (IL-10) changed unremarkably (P>0.05). Two patients experienced a transient fever lasting 4-6 hours and one felt a short time of fatigue after DC-CIK cells infusion. Conclusion: DC-CIK cells can kill 786-0 cells and K562 cells effectively. The DC-CIK cells infusion may improve immune response of some patients with a safe level, and it can be one of the assistant treatment methods for advanced RCC patients.
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Project supported by the Science and Technology Project of Suzhou (No. SS0524)