Cao Da-Yong, Yang Jing-Yue, Yue Shu-Qiang, Tao Kai-Shan, Song Zhen-Shun, Wang De-Sheng, Yang Yan-Ling, Dou Ke-Feng
Department of Hepatobiliary Surgery, State Key Discipline of Cell Biology, Xijing Hospital, Fourth Military Medical University, Shaanxi Province, China.
Cell Immunol. 2009;259(1):13-20. doi: 10.1016/j.cellimm.2009.05.007. Epub 2009 May 27.
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 (CTLs) 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.
在动物模型和人类临床试验中，患者来源的树突状细胞（DC）与自体肿瘤细胞的融合可诱导针对自体肿瘤的T细胞反应。这些融合细胞需要患者来源的肿瘤细胞，但并非总能获得。在此，我们将来自肝细胞癌（HCC）患者的自体DC与一种异基因HCC细胞系（HepG2）进行融合。这些融合细胞共表达肿瘤相关抗原（TAA）以及DC来源的共刺激分子和MHC分子。CD4(+)和CD8(+) T细胞均被融合细胞激活。融合细胞诱导产生的细胞毒性T淋巴细胞（CTL）能够通过HLA - A2和/或HLA - A24限制性机制杀伤自体HCC。针对共享TAA的CTL活性表明，同种异体抗原的存在并不妨碍具有杀伤自体HCC细胞活性的CTL的产生。这些融合细胞可能通过对共享肿瘤抗原的交叉启动在抗肿瘤免疫治疗中具有应用价值，并可能为过继性免疫治疗提供一个平台。
