期刊
CYTOTHERAPY
卷 18, 期 4, 页码 570-580出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.jcyt.2016.01.005
关键词
cancer vaccines; cell fusion; dendritic cells; hybrid cells; immunotherapy
类别
资金
- Sao Paulo Research Foundation-FAPESP [2009/54599-5, 2012/10939-0, 2013/26044-4]
- Brazilian National Council for Scientific and Technological Development-CNPq [830656/1999-5, 309556/2013-9]
- German Research Council [DFG/SFB738, DFG/REBIRTH-Unit 6.4]
Background aims. Dendritic cell (DC)-tumor cell hybrids have been used clinically in cancer immunotherapy, but their advantage over the simple mixture of tumor cells and DCs is still a matter of controversy. In this study, we compared DC-tumor cell hybrids with the non-fused mixture of DC and tumor cells directly in their ability to induce a specific immune response. Methods. Hybrids were obtained by electrofusion of tumor cells and monocyte-derived DCs. Cell phenotype was evaluated by flow cytometry and antigen-presenting ability by co-culture with syngeneic T cells followed by tetramer analysis and interferon (IFN)-gamma ELISPOT. Results. Less than half the cells in the mixture expressed DC co-stimulatory molecules. Furthermore, DCs in the mixture had significantly lower expression of MHC class I molecules than DCs in the fusion. Conversely, nearly all CD11c(+)Her2/neu(+) hybrids expressed CD80, CD86, CD83, HLA-DR and MHC class I from both tumor cells and DCs. Using tumor cells constitutively expressing a cytomegalovirus (CMV) antigen, we show that expansion of CMV-specific cytotoxic T lymphocytes (CTLs) restricted by DCs' MHC class I molecules was higher when DC-tumor hybrids were the stimulators. Furthermore, only hybrids stimulated CTLs to produce IFN-gamma in response to CMV-positive target cells. Conclusions. These data show the superiority of DC-tumor cell hybrids over their simple mixture as T-cell stimulators. Hybrids expressed more co-stimulatory and MHC molecules, induced higher antigen-specificT-cell expansion and were the only cells able to induce IFN-gamma-producing antigen-specific T cells. Thus, these data offer further support for cancer immunotherapeutic approaches using DC-tumor cell hybrids.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据