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多发性骨髓瘤中免疫原性抗原的血清学鉴定及生物信息学分析

Serological identification and bioinformatics analysis of immunogenic antigens in multiple myeloma.

作者信息

Zhou F L, Zhang W G, Chen G, Zhao W H, Cao X M, Chen Y X, Tian W, Liu J, Liu S H

机构信息

Department of Hematology, The Second Hospital, School of Medicine, Xi'an Jiaotong University, The west five road, No. 157, Xi'an 710004, China.

出版信息

Cancer Immunol Immunother. 2006 Aug;55(8):910-7. doi: 10.1007/s00262-005-0074-x. Epub 2005 Sep 29.

Abstract

Identifying appropriate tumor antigens is critical to the development of successful specific cancer immunotherapy. Serological analysis of tumor antigens by a recombinant cDNA expression library (SEREX) allows the systematic cloning of tumor antigens recognized by the spontaneous autoantibody repertoire of cancer patients. We applied SEREX to the cDNA expression library of cell line HMy2, which led to the isolation of six known characterized genes and 12 novel genes. Known genes, including ring finger protein 167, KLF10, TPT1, p02 protein, cDNA FLJ46859 fis, and DNMT1, were related to the development of different tumors. Bioinformatics was performed to predict 12 novel MMSA (multiple myeloma special antigen) genes. The prediction of tumor antigens provides potential targets for the immunotherapy of patients with multiple myeloma (MM) and help in the understanding of carcinogenesis. Crude lysate ELISA methodology indicated that the optical density value of MMSA-3 and MMSA-7 were significantly higher in MM patients than in healthy donors. Furthermore, SYBR Green real-time PCR showed that MMSA-1 presented with a high number of copy messages in MM. In summary, the antigens identified in this study may be potential candidates for diagnosis and targets for immunotherapy in MM.

摘要

识别合适的肿瘤抗原对于成功开展特异性癌症免疫治疗至关重要。通过重组cDNA表达文库对肿瘤抗原进行血清学分析(SEREX)能够系统克隆癌症患者自发自身抗体库所识别的肿瘤抗原。我们将SEREX应用于细胞系HMy2的cDNA表达文库,从而分离出6个已知特征基因和12个新基因。已知基因,包括泛素连接酶167、KLF10、TPT1、p02蛋白、cDNA FLJ46859 fis和DNMT1,与不同肿瘤的发生发展相关。利用生物信息学方法预测了12个新的多发性骨髓瘤特殊抗原(MMSA)基因。肿瘤抗原的预测为多发性骨髓瘤(MM)患者的免疫治疗提供了潜在靶点,并有助于理解肿瘤发生机制。粗裂解物ELISA方法表明,MM患者中MMSA - 3和MMSA - 7的光密度值显著高于健康供体。此外,SYBR Green实时定量PCR显示MMSA - 1在MM中呈现高拷贝数信息。总之,本研究中鉴定出的抗原可能是MM诊断的潜在候选物和免疫治疗的靶点。

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