Zhang Hong-Mei, Zhang Li-Wang, Liu Wen-Chao, Cheng Jie, Si Xiao-Ming, Ren Jun
Center of Clinical Oncology, Xijing Hospital, The Fourth Military Medical University, 15 Chang-Le West Road, Xi'an, People's Republic of China.
Cytotherapy. 2006;8(6):580-8. doi: 10.1080/14653240600991353.
DC vaccination with the use of tumor cells provides the potential to generate a polyclonal immune response to multiple known and unknown tumor Ag. Our study comparatively analyzed DC fused with tumor cells or transfected with tumor total RNA as potential cancer vaccines against hepatocellular carcinoma (HCC).
Immature DC generated from PBMC of patients with HCC were fused with HepG2-GFP (HepG2 cell line transfected stably with plasmid pEGFP-C3) cells or transfected with their total RNA. Matured DC were used to stimulate autologous T cells, and the resultant Ag-specific effector T cells were analyzed by IFN-gamma ELISPOT assay.
DC were capable of further differentiation into mature DC after fusion with HepG2-GFP cells or transfection with HepG2-GFP cell total RNA, and were able to elicit specific T-cell responses in vitro. Both methods of Ag loading could result in stimulating CD4+ and CD8+ T cells, but with the indication that fusion loading was more efficient than RNA loading in priming the Th1 response, while RNA loading was more effective in CTL priming.
Our results indicate that DC fused with tumor cells or transfected with tumor total RNA represent promising strategies for the development of cancer vaccines for treatment of HCC. They may have potential as an adjuvant immunotherapy for patients with HCC.
使用肿瘤细胞进行树突状细胞(DC)疫苗接种有可能引发针对多种已知和未知肿瘤抗原的多克隆免疫反应。我们的研究比较分析了与肿瘤细胞融合或用肿瘤总RNA转染的DC作为抗肝细胞癌(HCC)潜在癌症疫苗的情况。
从HCC患者外周血单核细胞(PBMC)中产生的未成熟DC与HepG2-GFP(稳定转染质粒pEGFP-C3的HepG2细胞系)细胞融合或用其总RNA转染。成熟的DC用于刺激自体T细胞,通过γ干扰素酶联免疫斑点分析(IFN-γ ELISPOT分析)对产生的抗原特异性效应T细胞进行分析。
DC与HepG2-GFP细胞融合或用HepG2-GFP细胞总RNA转染后能够进一步分化为成熟DC,并能够在体外引发特异性T细胞反应。两种抗原负载方法均可刺激CD4+和CD8+ T细胞,但有迹象表明,在启动Th1反应方面,融合负载比RNA负载更有效,而在启动细胞毒性T淋巴细胞(CTL)方面,RNA负载更有效。
我们的结果表明,与肿瘤细胞融合或用肿瘤总RNA转染的DC是开发用于治疗HCC的癌症疫苗的有前景的策略。它们可能作为HCC患者的辅助免疫疗法具有潜力。