Ren Jun, Jia Jun, Zhang Hongmei, Zhang Liwang, Ma Bo, Jiang Hanfang, Di Lijun, Song Guohong, Yu Jing
Department of Medical Oncology, Peking University School of Oncology/Beijing Cancer Hospital, No. 52 Fucheng Rd, Beijing, China 100036.
Cancer Sci. 2008 Jul;99(7):1420-6. doi: 10.1111/j.1349-7006.2008.00820.x. Epub 2008 Apr 16.
Dendritic cell (DC)-based immunotherapy is rapidly emerging as a promising treatment in cancer therapy. We had previously shown that DC pulsed with either defined mRNA of tumor antigen (Ag) such as alpha-fetoprotein (AFP), or total RNA of hepatocellular carcinoma (HCC) could elicit Ag-specific cytotoxic T lymphocyte (CTL) response. Therefore, we suggested a novel DC-based therapeutic method, in which DCs derived from CD34(+) cells enriched peripheral blood mononuclear cells were pulsed with liposome-coated AFP and mutant P53 (mtP53) fused gene pEGFP-C3/AFP-mtP53 to induce bi-targeted specific CTL responses against HCC. Three different genotype HCC cell lines, HepG2 (human histocompatibility leukocyte antigens (HLA) A2 positive, AFP expressing positive, P53 expressing negative), SMMC7721 (HLA A2 positive, neither AFP nor P53 expressing positive), and HMCC97 (HLA A2 positive, both AFP and P53 expressing positive) were selected as targets for CTL responses. An important finding was that DCs pulsed with the liposome-coated fused gene could evoke more intensive bi-targeted Ag-specific CTL responses against HMCC97 than DCs pulsed with either AFP or P53 single gene (P < 0.05). This experimental therapeutic model provides a new promising cytotherapeutic approach, in that DCs pulsed with the fused gene of different Ags might induce more extensive multitargeted antitumor immunity.
基于树突状细胞（DC）的免疫疗法正在迅速成为癌症治疗中一种有前景的治疗方法。我们之前已经表明，用肿瘤抗原（Ag）的特定mRNA（如甲胎蛋白（AFP））或肝细胞癌（HCC）的总RNA脉冲处理的DC可以引发Ag特异性细胞毒性T淋巴细胞（CTL）反应。因此，我们提出了一种基于DC的新型治疗方法，其中从富集外周血单核细胞的CD34(+)细胞衍生的DC用脂质体包被的AFP和突变型P53（mtP53）融合基因pEGFP-C3/AFP-mtP53进行脉冲处理，以诱导针对HCC的双靶点特异性CTL反应。选择三种不同基因型的HCC细胞系，HepG2（人类组织相容性白细胞抗原（HLA）A2阳性，AFP表达阳性，P53表达阴性）、SMMC7721（HLA A2阳性，AFP和P53均不表达阳性）和HMCC97（HLA A2阳性，AFP和P53均表达阳性）作为CTL反应的靶点。一个重要发现是，用脂质体包被的融合基因脉冲处理的DC比用AFP或P53单基因脉冲处理的DC能引发更强烈的针对HMCC97的双靶点Ag特异性CTL反应（P < 0.05）。这种实验性治疗模型提供了一种新的有前景的细胞治疗方法，即不同Ag的融合基因脉冲处理的DC可能诱导更广泛的多靶点抗肿瘤免疫。
