Comparative analysis of DC fused with allogeneic hepatocellular carcinoma cell line HepG2 and autologous tumor cells as potential cancer vaccines against hepatocellular carcinoma

Comparative analysis of DC fused with allogeneic hepatocellular carcinoma cell line HepG2 and autologous tumor cells as potential cancer vaccines against hepatocellular carcinoma
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DOI:
10.1016/j.cellimm.2009.05.007
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发表时间:
2009-01-01
影响因子:
4.3
通讯作者:
Dou, Ke-Feng
Dou, Ke-Feng
中科院分区:
医学4区
文献类型:
--
作者:
Cao, Da-Yong;Yang, Jing-Yue;Dou, Ke-Feng

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在动物模型和人类临床试验中,患者来源的树突状细胞 (DC) 和自体肿瘤细胞的融合诱导针对自体肿瘤的 T 细胞反应。这些融合细胞需要来自患者的肿瘤细胞,然而,这些细胞并不总是可用的。在这里,我们将来自肝细胞癌 (HCC) 患者的自体 DC 与同种异体 HCC 细胞系 (HepG2) 融合。这些融合细胞共表达肿瘤相关抗原 (TAA) 和 DC 衍生的共刺激分子和 MHC 分子。 CD4(+)和CD8(+)T细胞均被融合细胞激活。由融合细胞诱导的细胞毒性T淋巴细胞(C7L)能够通过HLA-A2和/或HLA-A24限制机制杀死自体HCC。针对共享 TAA 的 CTL 活性表明,同种异体抗原的存在不会阻止具有针对自体 HCC 细胞活性的 CTL 的发育。这些融合细胞可能通过针对共享肿瘤抗原的交叉引发而在抗肿瘤免疫治疗中得到应用,并可能为过继免疫治疗提供平台。 Crown 版权所有 (C) 2009 由 Elsevier Inc. 出版。保留所有权利。
Fusions of patient-derived dendritic cells (DCs) and autologous tumor cells induce T-cell responses against autologous tumors in animal models and human clinical trials. These fusion cells require patient-derived tumor cells, which are not, however, always available. Here we fused autologous DCs from patients with hepatocellular carcinoma (HCC) to an allogeneic HCC cell line (HepG2). These fusion cells co-expressed tumor-associated antigens (TAAs) and DC-derived costimulatory and MHC molecules. Both CD4(+) and CD8(+) T cells were activated by the fusion cells. Cytotoxic T lymphocytes (C7Ls) induced by the fusion cells were able to kill autologous HCC by HLA-A2- and/or HLA-A24-restricted mechanisms. CTL activity against shared TAAs indicates that the presence of alloantigens does not prevent the development of CTLs with activity against autologous HCC cells. These fusion cells may have applications in anti-tumor immunotherapy through cross-priming against shared tumor antigens and may provide a platform for adoptive immunotherapy. Crown Copyright (C) 2009 Published by Elsevier Inc. All rights reserved.