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鉴定食管癌中源自癌症睾丸抗原 MAGE-4 的新型 CD8+ T 细胞表位。

Identification of a novel CD8+ T cell epitope derived from cancer-testis antigen MAGE-4 in oesophageal carcinoma.

机构信息

Department of Bioengineering, Zhengzhou University, Zhengzhou, China.

出版信息

Scand J Immunol. 2011 Dec;74(6):561-7. doi: 10.1111/j.1365-3083.2011.02606.x.

Abstract

MAGE-4 is considered as an attractive cancer-testis (CT) antigen for tumour immunotherapy, and it is overexpressed in oesophageal carcinoma (EC). To identify MAGE-4-derived HLA-A2 restricted epitopes, native peptides and their analogues were predicted with prediction programs. The native peptide, p286 (KVLEHVVRV), and its analogues, p286-1Y2L and p286-1Y2L9L, showed potent binding affinity and stability towards HLA-A*0201 molecule. Cytotoxic T lymphocytes (CTLs) induced by p286-1Y2L9L could release IFN-γ in ELISPOT assay. In cytotoxicity assay, p286-1Y2L9L showed the capability to induce specific CTLs which could lyse the target cancer cells from both PBMCs of healthy donors and HLA-A2.1/K(b) transgenic mice. Our results indicated that the peptide p286-1Y2L9L could serve as a novel candidate epitope to develop peptide vaccines against oesophageal carcinoma.

摘要

MAGE-4 被认为是一种有吸引力的癌症睾丸(CT)抗原,用于肿瘤免疫治疗,在食管癌(EC)中过度表达。为了鉴定 MAGE-4 衍生的 HLA-A2 限制性表位,使用预测程序预测天然肽及其类似物。天然肽 p286(KVLEHVVRV)及其类似物 p286-1Y2L 和 p286-1Y2L9L 对 HLA-A*0201 分子具有很强的结合亲和力和稳定性。p286-1Y2L9L 诱导的细胞毒性 T 淋巴细胞(CTL)在 ELISPOT 测定中可以释放 IFN-γ。在细胞毒性测定中,p286-1Y2L9L 显示出诱导特异性 CTL 的能力,这些 CTL 可以裂解来自健康供体和 HLA-A2.1/K(b)转基因小鼠的 PBMC 中的靶癌细胞。我们的结果表明,肽 p286-1Y2L9L 可以作为一种新型候选表位,用于开发针对食管癌的肽疫苗。

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