Cytotoxic T cell responses are enhanced by antigen design involving the presentation of MUC1 peptide on cholera toxin B subunit
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Wuguang Lu1,2,5, Lingchong Qiu1, Zhanpeng Yan2,5, Zhibing Lin1, Meng Cao2,5, Chunping Hu2,5, Zhigang Wang2,5, Jin Wang3, Ye Yu3, Xiaoyang Cheng3, Peng Cao2,5, Rongxiu Li1,4
1State Key Laboratory of Microbial Metabolism, School of Life Sciences & Biotechnology, Shanghai Jiao Tong University, Shanghai, 200240, China
2Laboratory of Cellular and Molecular Biology, Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210028, China
3Institute of Medical Science and Department of Pharmacology and Physiology, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China
4Engineering Research Center of Cell & Therapeutic Antibody, Ministry of Education, School of Pharmacy, Shanghai Jiao Tong University, Shanghai, 200240, China
5Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing 210028, China
Rongxiu Li, e-mail: [email protected]
Peng Cao, e-mail: [email protected]
Keywords: immunotherapy, MUC1, antigen design, cytotoxic T cell response, vaccine
Received: March 22, 2015 Accepted: September 08, 2015 Published: September 21, 2015
Induction of cytotoxic T lymphocytes (CTL) is critical to cancer vaccine based immunotherapy. Efforts to elicit CTLs against tumor MUC1 with peptide based vaccine have not been successful in clinical application. We have design a MUC1 vaccine by replacing B cell epitope of CTB with MUC1 VNTR peptide. Immunization with hybrid CTB-MUC1 plus aluminum hydroxide and CpG adujuvant (CTB-MUC1-Alum-CpG) induce MUC1-specific CTLs in mice. Moreover, this vaccination can prevent tumor growth and reduce tumor burden in MUC1+B16 mice model. Meanwhile, CTB-MUC1-Alum-CpG vaccination can promote Th1 cells and CD8+ T cells inflate to tumor tissue. Our approach might be applicable to other cancer vaccine design.
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