Cytotoxic T cell responses are enhanced by antigen design involving the presentation of MUC1 peptide on cholera toxin B subunit

// Wuguang Lu 1, 2, 5 , Lingchong Qiu 1 , Zhanpeng Yan 2, 5 , Zhibing Lin 1 , Meng Cao 2, 5 , Chunping Hu 2, 5 , Zhigang Wang 2, 5 , Jin Wang 3 , Ye Yu 3 , Xiaoyang Cheng 3 , Peng Cao 2, 5 , Rongxiu Li 1, 4 1 State Key Laboratory of Microbial Metabolism, School of Life Sciences & Biotechnology, Shanghai Jiao Tong University, Shanghai, 200240, China 2 Laboratory of Cellular and Molecular Biology, Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210028, China 3 Institute of Medical Science and Department of Pharmacology and Physiology, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China 4 Engineering Research Center of Cell & Therapeutic Antibody, Ministry of Education, School of Pharmacy, Shanghai Jiao Tong University, Shanghai, 200240, China 5 Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing 210028, China Correspondence to: Rongxiu Li, e-mail: rxli@sjtu.edu.cn Peng Cao, e-mail: pcao79@yahoo.com Keywords: immunotherapy, MUC1, antigen design, cytotoxic T cell response, vaccine Received: March 22, 2015      Accepted: September 08, 2015      Published: September 21, 2015 ABSTRACT 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.