Immunotherapy of Epstein-Barr Virus Associated Malignancies Using Mycobacterial HSP70 and LMP2A356-364 Epitope Fusion Protein  

作　　者：Genyan Liu Kun Yao Bing Wang Yun Chen Feng Zhou Yidi Guo Jian Xu Hongzhen Shi 

机构地区：[1]Department of Microbiology and Immunology,Nanjing Medical University,Nanjing 210029,China [2]Department of Laboratory Medicine,the First Affiliated Hospital of Nanjing Medical University,Nanjing 210029,China [3]Nanjing Dekang BioTechnologies Co.,Ltd.Nanjing 211100,China

出　　处：《Cellular & Molecular Immunology》2009年第6期423-431,共9页中国免疫学杂志（英文版）

基　　金：This work was funded by the National Natural Science Foundation of China(No.30170880 and No.30571715);Science Committee Foundation of Jiangsu Province(No.BJ98100);Project of Key Laboratory of Laboratory Diagnosis of Jiangsu Province(No.XK200731).

摘　　要：Epstein-Barr virus infection is strongly associated with a number of malignancies.The EBV latent membrane protein 2A has been implicated as one of the most attractive candidates for immunotherapy of related malignancies.In previous studies,the T cell epitopes of LMP2A have been identified systematically.However,the epitope-based vaccine generally meets inefficient immunogenicity when used in vivo directly,which could be overcome by combination with appropriate adjuvants.Heat shock protein is a natural chaperon,which is able to activate the classical major histocompatibility complex class I antigen-processing pathway(cross-presentation).In this study,a minigene encoding LMP2A356-364(FLYALALLL)was genetically fused to the carboxy-terminal of mycobacterial heat shock protein 70.The epitope fusion protein was expressed and purified,and the cross-presentation of LMP2A_(356-364) by monocyte-derived dendritic cells pulsed with the epitope fusion protein was evaluated.Results showed that the epitope fusion protein-pulsed mDCs were much more efficient than the single peptide-pulsed mDCs on CTL activation.Immunization of HLA-A2.1 transgenic mice with MtHsp70-LMP2A_(356-364) generated peptide specific CTL more effectively than a single peptide plus incomplete Freund's adjuvant(IFA).Growth of LMP2A expressing B16 melanoma tumor cells was suppressed in the vaccinated groups.Our results suggested that MtHsp70-LMP2A_(356-364) fusion protein was more effective than the CD8^(+)T cell epitope alone on anti-tumor immunity.As a result,the MtHsp70-LMP2A_(356-364) fusion protein is considered to be a promising candidate vaccine for EBV related malignancies.

关 键 词：mycobacterial heat shock protein 70 Epstein-Barr virus latent membrane protein 2A EPITOPE cytotoxic T-lymphocytes 

分 类 号：R73[医药卫生—肿瘤]