Patient-derived dendritic cells transduced with an α-fetoprotein-encoding adenovirus and co-cultured with autologous cytokine-induced lymphocytes induce a specific and strong immune response against hepatocellular carcinoma cells
Patient-derived dendritic cells transduced with an α-fetoprotein-encoding adenovirus and co-cultured with autologous cytokine-induced lymphocytes induce a specific and strong immune response against hepatocellular carcinoma cells
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DOI：
10.1111/j.1478-3231.2005.01235.x
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发表时间：
2006-04-01
影响因子：
6.7
通讯作者：
Caselmann, WH
中科院分区：
文献类型：
--
作者：
González-Carmona, MA;Märten, A;Caselmann, WH
背景/目的：打破对肝细胞癌（HCC）相关甲胎蛋白（AFP）抗原的免疫耐受是可能的。利用这种潜力治疗免疫功能低下的肝癌患者是有限的。在这项研究中，我们分析了是否树突状细胞（DC）从肝癌患者转导人AFP（hAFP）表达腺病毒和共培养的苦参碱诱导的杀伤细胞（CIK）细胞可以诱导一个强大的特异性免疫反应对肝癌细胞。方法：制备hAFP腺病毒（Ad-hAFP）。来自健康供体或患者的DC以非常高的效率转导。然后，将DC与自体CIK细胞共培养，并分析其裂解HCC细胞的能力。结果：AFP转导的DC能强烈刺激CIK细胞裂解约70%的AFP表达的HCC细胞。当淋巴细胞与Ad-hAFP转导的DC共培养时，细胞毒性显著高于Ad-mock转导的DC，表明AFP特异性免疫应答。更有趣的是，来自AFP阳性HCC患者的CIK细胞可以被刺激以与来自健康个体的CIK细胞一样有效地裂解AFP表达的HCC细胞，并且比来自没有AFP表达的HCC患者的CIK细胞更强。结论：数据表明，用表达AFP的腺病毒转导并与自体CIK细胞共培养的患者来源的DC诱导针对HCC细胞的AFP特异性强免疫应答。因此，这种方法可能具有用于HCC患者的过继性和/或基于DC的免疫疗法的潜力。
Background/Aims: Breaking immunologic tolerance towards the hepatocellular carcinoma (HCC)-associated alpha-fetoprotein (AFP) antigen is possible. The use of this potential for the treatment of immunocompromised HCC patients is limited. In this study, we analyzed whether dendritic cells (DCs) from HCC patients transduced with a human AFP (hAFP)-expressing adenovirus and co-cultured with cytokine-induced killer (CIK) cells can induce a strong specific immune response against HCC-cells. Methods: An hAFP-encoding adenovirus (Ad-hAFP) was generated. DCs from healthy donors or patients were transduced at a very high efficacy. Afterwards, DCs were co-cultured with autologous CIK-cells, and their ability to lyse HCC-cells was analyzed. Results: AFP-transduced DCs stimulated CIK cells strongly to lyse about 70% of AFP-expressing HCC cells. Cytotoxicity was significantly higher when lymphocytes were co-cultured with Ad-hAFP-transduced DCs than with Ad-mock-transduced DCs, indicating an AFP-specific immune response. More interestingly, CIK cells from patients with AFP-positive HCC could be stimulated to lyse AFP-expressing HCC cells as effectively as CIK cells from healthy individuals and stronger than CIK cells from patients without AFP-expressing HCC. Conclusions: The data demonstrate that patient-derived DCs that were transduced with an AFP-expressing adenovirus and co-cultured with autologous CIK cells induce an AFP-specific, strong immune response against HCC cells. Therefore, this approach may have a potential for an adoptive and/or DC-based immunotherapy for HCC patients.