Developing Effective Cancer Vaccines Using Rendered-Inactive Tumor Cells

被引:2
|
作者
Zhao, Shushu [1 ]
Wu, Shuting [1 ]
Jiang, Sheng [1 ]
Zhao, Gan [1 ]
Wang, Bin [1 ,2 ]
机构
[1] Fudan Univ, Sch Basic Med Sci, Key Lab Med Mol Virol, Shanghai 200032, Peoples R China
[2] Fudan Univ, Shanghai Inst Infect Dis & Biosecur, Shanghai 200032, Peoples R China
关键词
tumor-cell-based vaccine; inactivated tumor cells; antitumor growth; regulatory T cells; anti-CD25; antibody; REGULATORY T-CELLS; DENDRITIC CELLS; BLOCKADE; IMMUNITY;
D O I
10.3390/vaccines11081330
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Cancer is a major public health threat, and researchers are constantly looking for new ways to develop effective treatments. One approach is the use of cancer vaccines, which work by boosting the body's immune system to fight cancer. The goal of this study was to develop an effective cancer vaccine using rendered-inactive tumor cells. A CMS5 fibrosarcoma tumor model in BALB/c mice and an E.G7 lymphoma tumor model in C57BL/6 mice were used to evaluate how mitomycin C-inactivated tumor cells mediated tumor protection. The results showed that immunization with inactivated CMS5 cells significantly improved tumor suppression after a challenge with live CMS5 tumor cells, but no effect was observed using the E.G7 tumor model. The results suggested that DC (dendritic cell) responses to tumor antigens are critical. The maturation and activation of DCs were effectively promoted by mitomycin C-treated CMS5 cells, as well as enhanced phagocytosis ability in vitro. The tumor-protective effects established by the vaccination of inactivated CMS5 cells were CD8+ T cell-dependent, as the antitumor responses disappeared after eliminating CD8+ T cells. It was found that the tumor-prevention efficacy was dramatically increased by combining inactivated CM55 tumor cells with anti-CD25 antibodies to temporarily deplete Treg cells (regulatory T cells). This strategy could also significantly induce the rejection against E.G7 tumors. In addition, vaccination with anti-CD25 antibodies plus inactivated CMS5 cells elicited antitumor responses against heterologous tumors. According to the findings of this study, combining the immunization of inactivated tumor cells with an anti-CD25 antibody may be an effective method for cancer prevention.
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页数:12
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