Identification of a novel HLA-A2-restricted mutated Survivin epitope and induction of specific anti-HCC CTLs that could effectively cross-recognize wild-type Survivin antigen

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• 作者：Han Shen (1) (2)
  Hong-Wei Shao (1) (3)
  Xiao-Hua Chen (4)
  Feng-Lin Wu (1) (3)
  Hui Wang (1) (3)
  Zhao-Liang Huang (1)
  Juan Shen (1)
  Teng Wang (1)
  Wen-Feng Zhang (1) (3)
  Shu-Lin Huang (1) (3)
  
• 关键词：Cross ; recognition ; HCC ; Survivin ; Point ; mutation peptide ; CTL
• 刊名：Cancer Immunology, Immunotherapy
• 出版年：2013
• 出版时间：February 2013
• 年：2013
• 卷：62
• 期：2
• 页码：393-403
• 全文大小：750KB
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• 作者单位：Han Shen (1) (2)
  Hong-Wei Shao (1) (3)
  Xiao-Hua Chen (4)
  Feng-Lin Wu (1) (3)
  Hui Wang (1) (3)
  Zhao-Liang Huang (1)
  Juan Shen (1)
  Teng Wang (1)
  Wen-Feng Zhang (1) (3)
  Shu-Lin Huang (1) (3)
  
  1. School of Life Science and Biopharmaceutics, Guangdong Pharmaceutical University, 28 E. Rd outside the City of Guangzhou University, Guangzhou, 510006, Guangdong, People’s Republic of China
  2. Southern Medical University, 1838 North Guangzhou Avenue, Guangzhou, 510515, Guangdong, People’s Republic of China
  3. Institute of Bio-Pharmaceutical, Guangdong Pharmaceutical University, 28 E. Rd outside the City of Guangzhou University, Guangzhou, 510006, Guangdong, People’s Republic of China
  4. Department of Oncology, Guangzhou Panyu Central Hospital, 8 Fuyu Road East, Panyu District, Guangzhou, 511400, Guangdong, People’s Republic of China
  
• ISSN：1432-0851

文摘

Peptide vaccine based on tumor-associated antigen (TAA), which usually belongs to self-antigen with poor immunogenicity, has been considered as an attractive option for treatment of malignant tumors. The ideal TAA epitopes should have stable affinity to major histocompatibility complex (MHC) molecules and elicit strong anti-tumor immune response. Although point-mutation technology of TAA peptide may increase the binding capability to MHC molecules, some previous studies have revealed that part of the variant peptides results in lymphocyte not to effectively cross-recognize and kill the target tumor expressed wild-type TAA. Here, we designed a novel HLA-A2-restricted mutated TAA Survivin epitope nonapeptide Sur79L2 (KLSSGCAFL) that showed higher binding ability compared to wild-type peptide Sur79 (KHSSGCAFL) in T2-binding assays. To investigate whether Sur79L2 can induce Survivin-specific anti-hepatocellular carcinoma (HCC) response, we stimulated tumor-associated lymphocytes from a HCC patient with Sur79L2 in vitro. IFN-γ release and cytotoxicity assays showed Sur79L2 could effectively cross-recognize and lysis T2 cell plus peptide Sur79 and HCC cell lines (expression of wild-type Survivin antigen) in an HLA-A2-restricted manner. In contrast, peptide Sur95 (ELTLGEFLKL) that has been reported as a very promising anti-tumor epitope in a variety of tumors except HCC were not able to generate detectable cytotoxic immune responses against HCC in this study. Our results suggest that point-mutated peptide Sur79L2 is a new HLA-A2-restricted CTL epitope and may be useful for the immunotherapy for patients with HCC.