Sun Yi, Chen Jian, Cai Peng, Hu Yong-He, Zhong Guo-Cheng, Feng Huai-Zhi, Min Min, Li Shuo, Zhang Cong
Department of Oncology and Hematology, The 452nd Hospital of Chinese PLA, Chengdu 610021, Sichuan Province, China.
Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2010 Feb;18(1):219-23.
This study was aimed to investigate the killing activity of cytokine-induced killer (CIK) cells after being incubated with autologous tumor cell lysate-pulsed dendritic cells (DC) and to evaluate the clinical efficacy and side effect of autologous tumor cell lysate-loaded DC in combination with CIK on relapsed or refractory non-Hodgkin's lymphoma (NHL). Peripheral blood mononuclear cells (PBMNC) were isolated from 9 patients with NHL, and cultured with granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4) to produce DC. The DC were pulsed with autologous tumor cell lysate. T lymphocytes from PBMNC were cultured with interferon-gamma (IFN-gamma), IL-2, CD3-moAb, and IL-1alpha to prepare CIK. After receiving the immunotherapy of DC and CIK, immunologic and clinical responses were evaluated. The results showed that the AgNOR, CD3(+)CD8(+) and CD3(+)CD56(+) ratio were markedly improved after the immunotherapy (p < 0.01); IFN-gamma and IL-12 levels in supernatant of DC-CIK group were higher than that in CIK group (p < 0.01); Tumor size were significantly decreased after the immunotherapy (p < 0.05). Except transient fever and chill, no remarkable adverse event happened during or after the treatment. It is concluded that the autologous tumor cell lysate-pulsed DC in combination with CIK show ability to specifically kill the lymphoma cells, obviously increases the IS value of Ag-NOR in peripheral lymphocytes, secretes cytokines higher than CIK cells alone. This combination displays the short-term satisfied efficacy on NHL through inducing specific antitumor immunity, and can be used as an effective adjuvant measure for the routine therapy of NHL.
本研究旨在探讨细胞因子诱导的杀伤细胞（CIK）与自体肿瘤细胞裂解物脉冲树突状细胞（DC）共孵育后的杀伤活性，并评估自体肿瘤细胞裂解物负载的DC联合CIK对复发或难治性非霍奇金淋巴瘤（NHL）的临床疗效及副作用。从9例NHL患者中分离外周血单个核细胞（PBMNC），并用粒细胞-巨噬细胞集落刺激因子（GM-CSF）和白细胞介素-4（IL-4）培养以产生DC。DC用自体肿瘤细胞裂解物脉冲。PBMNC中的T淋巴细胞用干扰素-γ（IFN-γ）、IL-2、CD3单克隆抗体和IL-1α培养以制备CIK。接受DC和CIK免疫治疗后，评估免疫和临床反应。结果显示，免疫治疗后嗜银蛋白（AgNOR）、CD3(+)CD8(+)和CD3(+)CD56(+)比例显著改善（p < 0.01）；DC-CIK组上清液中IFN-γ和IL-12水平高于CIK组（p < 0.01）；免疫治疗后肿瘤大小显著减小（p < 0.05）。除短暂发热和寒战外，治疗期间及治疗后未发生明显不良事件。结论是，自体肿瘤细胞裂解物脉冲的DC联合CIK显示出特异性杀伤淋巴瘤细胞的能力，明显增加外周淋巴细胞中Ag-NOR的IS值，分泌的细胞因子高于单独的CIK细胞。这种联合通过诱导特异性抗肿瘤免疫对NHL显示出短期满意的疗效，可作为NHL常规治疗的有效辅助措施。
