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树突状细胞与同种异体肝癌细胞系融合与融合自体肿瘤细胞作为肝癌疫苗的比较。

Dendritic cells fused with allogeneic hepatocellular carcinoma cell line compared with fused autologous tumor cells as hepatocellular carcinoma vaccines.

机构信息

Department of Clinical Oncology, State Key Discipline of Cell Biology, Xijing Hospital, Fourth Military Medical University, Xian, Shaanxi, China.

出版信息

Hepatol Res. 2010 May;40(5):505-13. doi: 10.1111/j.1872-034X.2010.00625.x. Epub 2010 Mar 30.

Abstract

PURPOSE

To investigate the specific antitumor responses against autologous hepatocellular carcinoma (HCC) cells of dendritic cells (DCs) fused with allogeneic HCC cell line, and evaluated the feasibility of BEL7402 as an alternative strategy to deliver shared HCC antigens to DCs.

METHODS

Previous studies demonstrated fusions of patient-derived DCs and autologous tumor cells could induce T-cell responses against autologous tumors. These fusion cells require patient-derived tumor cells, which are not, however, always available. Here, we report the fusing of autologous DCs with allogeneic HCC cell line to induced cytotoxic T-lymphocyte (CTL) response against autologous HCC cells compare with autologous tumor cells.

RESULTS

These DC/ BEL7402 fusion cells co-expressed tumor-associated antigens and DC-derived costimulatory and major histocompatibility complex molecules. Both CD4+ and CD8 T+ cells were activated by the fusion cells as demonstrated by the proliferation of T-cells, the production of cytokines and the simultaneous induction of specific CTL responses. Significantly, CTL induced by dendritic cell/allogeneic BEL7402 fusion cells were able to kill autologous HCC cells by human leukocyte antigen-A2 restricted mechanisms. The results did not show significant difference between DC fusion with autologous hepatocellular carcinoma cells and DC fusion with allogeneic hepatocellular carcinoma cell line.

CONCLUSIONS

The fusion of allogeneic HCC cell line and autologous DCs may have applications in antitumor immunotherapy through cross-priming against shared tumor antigens and may provide a platform for adoptive immunotherapy.

摘要

目的

研究树突状细胞(DC)与同种异体肝癌细胞系融合后对自体肝癌细胞的特异性抗肿瘤反应,并评估 BEL7402 作为向 DC 递呈共享肝癌抗原的替代策略的可行性。

方法

先前的研究表明,源自患者的 DC 与自体肿瘤细胞融合可诱导针对自体肿瘤的 T 细胞反应。这些融合细胞需要源自患者的肿瘤细胞,但并非总是可获得。在这里,我们报告了自体 DC 与同种异体肝癌细胞系的融合,以诱导针对自体肝癌细胞的细胞毒性 T 淋巴细胞(CTL)反应,并与自体肿瘤细胞进行比较。

结果

这些 DC/BEL7402 融合细胞共表达肿瘤相关抗原和 DC 来源的共刺激和主要组织相容性复合体分子。T 细胞的增殖、细胞因子的产生以及特异性 CTL 反应的同时诱导表明 CD4+和 CD8+T 细胞均被融合细胞激活。值得注意的是,树突状细胞/同种异体 BEL7402 融合细胞诱导的 CTL 通过人类白细胞抗原-A2 限制机制能够杀伤自体肝癌细胞。DC 与自体肝癌细胞融合与 DC 与同种异体肝癌细胞系融合的结果没有显著差异。

结论

同种异体肝癌细胞系与自体 DC 的融合可能通过交叉呈递共享肿瘤抗原在抗肿瘤免疫治疗中具有应用价值,并为过继免疫治疗提供了一个平台。

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