In vivo enhancement of the MAGE-specific cellular immune response by a recombinant MAGE1-MAGE3-TBHSP70 tumor vaccine

重组 MAGE1-MAGE3-TBHSP70 肿瘤疫苗在体内增强 MAGE 特异性细胞免疫反应

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作者:Wang Junwei #, Zhan Xiumin #, Ye Jing, Yang Shoujing, Li Zengshan

Background

Since cytotoxic T cell (CTL) response is the major cellular type in attacking tumor cells, most immunotherapy targets to manipulate the CTL response. Immunotherapies targeting melanoma-specific antigens (MAGEs), a group of tumor-specific shared antigen, have shown to be promising. Our previous study has shown that MAGE1/TBHSP70 and MAGE3/TBHSP70 could induce a robust immune response against B-16 melanoma cells in C57BL/6 mice. In this study, we used an animal model to further demonstrate MAGEs as a potential immunotherapy target for tumorigenesis in vivo.

Conclusion

This newly-developed recombinant protein vaccine may serve as a new immunotherapy for cancer.

Methods

In the current study, we developed a MAGE1/MAGE3/TBHSP70 recombinant protein vaccine and evaluated its protective efficacy against tumor development by challenge vaccine-immunized mice with MAGE-expressing human tumor cell lines in a Hu-PBL-SCID mouse model. The cellular immune reactions were monitored by ELISPOT and cytotoxicity assays.

Results

Splenocytes isolated from vaccine-immunized mice presented potent cytokine secretion capacity and CTL-specific cytotoxic. Vaccine-immunized mice had a significant tumor regression and prolonged survival compared with controls (both p < 0.05). In vitro, rMAGE1-MAGE3-TBHSP70 showed a potent tumor-antigen-specific immune response in both hepatocellular carcinoma and pulmonary carcinoma cell lines.

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