CpG寡核苷酸
CpG站点
免疫学
树突状细胞
免疫疗法
癌症研究
癌症免疫疗法
医学
仙台病毒
免疫
免疫系统
生物
病毒
基因表达
DNA甲基化
基因
生物化学
作者
Kazuo Hiraoka,Seiji Yamamoto,Satoru Otsuru,S. Nakai,Katsuto Tamai,Ryuichi Morishita,Toshio Ogihara,Yasufumi Kaneda
出处
期刊:Journal of Immunology
[The American Association of Immunologists]
日期:2004-10-01
卷期号:173 (7): 4297-4307
被引量:48
标识
DOI:10.4049/jimmunol.173.7.4297
摘要
Immunization with dendritic cells (DCs) using various Ag-loading approaches has shown promising results in tumor-specific immunotherapy and immunoprevention. Fused cells (FCs) that are generated from DCs and tumor cells are one of effective cancer vaccines because both known and unknown tumor Ags are presented on the FCs and recognized by T cells. In this study, we attempted to augment antitumor immunity by the combination of DC-tumor FC vaccination with immunostimulatory oligodeoxynucleotides containing CpG motif (CpG ODN). Murine DCs were fused with syngeneic tumor cells ex vivo using inactivated hemagglutinating virus of Japan (Sendai virus). Mice were intradermally (i.d.) immunized with FCs and/or CpG ODN. Coadministration of CpG ODN enhanced the phenotypical maturation of FCs and unfused DCs, and the production of Th1 cytokines, such as IFN-gamma and IL-12, leading to the induction of tumor-specific CTLs without falling into T cell anergy. In addition, immunization with FCs + CpG ODN provided significant protection against lethal s.c. tumor challenge and spontaneous lung metastasis compared with that with either FCs or CpG ODN alone. Furthermore, among mice that rejected tumor challenge, the mice immunized with FCs + CpG ODN, but not the mice immunized with FCs or CpG ODN alone, completely rejected tumor rechallenge, indicating that CpG ODN provided long-term maintenance of tumor-specific immunity induced by FCs. Thus, the combination of DC-tumor FCs and CpG ODN is an effective and feasible cancer vaccine to prevent the generation and recurrence of cancers.
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