Wang Junwei1, Zhan Xiumin1, Ye Jing1, Yang Shoujing1, Li Zengshan1,2. 1. The State Key Laborotary of Cancer Biology, Xijing Hospital of the Fourth Military Medical University, Xi'an, 710032 Shanxi China. 2. The Pathology Department, Fourth Military Medical University, ChangLe West Road 17, Xi'an, 710032 Shanxi China.
Abstract
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. 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. CONCLUSION: This newly-developed recombinant protein vaccine may serve as a new immunotherapy for cancer.
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. 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 humantumor cell lines in a Hu-PBL-SCIDmouse 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. CONCLUSION: This newly-developed recombinant protein vaccine may serve as a new immunotherapy for cancer.
Entities:
Keywords:
Cytotoxic T cell response; Immunotherapy; Melanoma-specific antigens; Vaccine
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