Zhang Xiu-Min, Zhang Yun-Fei, Huang Yang, Qu Ping, Ma Bin, Si Shao-Yan, Li Zeng-Shan, Li Wen-Xin, Li Xia, Ge Wei, Hu Pei-Zhen, Sui Yan-Fang
State Key Laboratory of Cancer Biology, Department of Pathology, Xijing Hospital, Fourth Military Medical University, Shaanxi Province 710032, P.R. China.
Oncol Rep. 2008 Jul;20(1):245-52.
Tumor antigen-derived peptides have been widely used to elicit tumor-specific cytotoxic T lymphocytes (CTLs). MAGE gene products are of particular interest owing to their wide expression in many tumors and their potential to induce tumor-specific CTL responses. Antigen-specific CTLs induced by MAGE gene-derived peptides have proven to be highly efficacious in the prevention and treatment of various types of tumors. MAGE-3 has been used as a target for tumor immunotherapy. MAGE-n is a new member of the MAGE gene family and has been shown to be closely associated with hepatocellular carcinoma (HCC). However, the majority of previous investigations focused on the single MAGE antigen-derived peptides as a cancer vaccine which has many limitations. The tumor antigen expression is known to be heterogeneous and tumor cells can express multiple tumor antigens. Thus, vaccines incorporating single antigen-derived epitopes may be inadequate in generating a complete immune response against the tumor. Instead, a polyvalent vaccine incorporating epitopes derived from several tumor antigens may be more effective. Our study combined the MAGE-3 and MAGE-n-derived peptides as a cancer vaccine. The results showed that the combination of MAGE-3 and MAGE-n epitopes induced more effective anti-tumor immune responses than either of the peptides alone. In addition, the peptide-specific activity was observed to be in an MHC-restricted manner. Our study indicated that the combination of several tumor antigen-derived peptides may present a better peptide-based cancer immunotherapy.
肿瘤抗原衍生肽已被广泛用于引发肿瘤特异性细胞毒性T淋巴细胞(CTL)。MAGE基因产物因其在许多肿瘤中的广泛表达以及诱导肿瘤特异性CTL反应的潜力而备受关注。由MAGE基因衍生肽诱导的抗原特异性CTL已被证明在预防和治疗各种类型的肿瘤方面具有高效性。MAGE-3已被用作肿瘤免疫治疗的靶点。MAGE-n是MAGE基因家族的新成员,已被证明与肝细胞癌(HCC)密切相关。然而,先前的大多数研究集中在单一MAGE抗原衍生肽作为癌症疫苗,这存在许多局限性。已知肿瘤抗原表达具有异质性,肿瘤细胞可表达多种肿瘤抗原。因此,包含单一抗原衍生表位的疫苗可能不足以产生针对肿瘤的完整免疫反应。相反,包含来自几种肿瘤抗原的表位的多价疫苗可能更有效。我们的研究将MAGE-3和MAGE-n衍生肽组合作为癌症疫苗。结果表明,MAGE-3和MAGE-n表位的组合比单独的任何一种肽诱导出更有效的抗肿瘤免疫反应。此外,观察到肽特异性活性是以MHC限制的方式。我们的研究表明,几种肿瘤抗原衍生肽的组合可能提供更好的基于肽的癌症免疫疗法。