Zhou Shengtao, Yi Tao, Zhang Boya, Huang Fuqiang, Huang Huiqiong, Tang Jing, Zhao Xia
Department of Gynecology and Obstetrics, West China Second Hospital, Sichuan University, Chengdu 610041, P.R. China.
Comb Chem High Throughput Screen. 2012 Mar;15(3):202-15. doi: 10.2174/138620712799218572.
Advances in novel tumor-associated antigen (TAA) screening strategy have accelerated the identification and characterization of biomarkers and potential target molecules for tumor subtyping, diagnosis and therapeutics, which may facilitate early detection and diagnosis of the diseases individually and enhance treatment approaches for cancer. Over the past decades, a plethora of non-invasive methodologies dedicated to identify novel target molecules have been primarily focusing on the discovery of human tumor antigens recognized by the autologous antibody repertoire or cytotoxic T lymphocytes, among which serological analysis of recombinant cDNA expression libraries (SEREX) technology is chronologically first established and is of outstanding sensitivity and antigen coverage. This approach involves immunoscreening cDNA libraries extracted from fresh tumor tissues with sera from cancer patients to identify gene products recognized by IgG antibody. SEREX-defined clones can be directly sequenced and their expression profiles can be readily determined, allowing for immediate structural definition of the antigenic target and subsequent identification of TAAs and their cognate autoantibodies. This review is not only devoted to outline the SEREX technology and its advantages, drawbacks and recent modifications currently available for discovering provocative tumor antigens, but also to translate these SEREX-defined peptides into valuable cancer-specific signatures that would aid in the development of diagnostics, prognostics and therapeutics for cancer patients.
新型肿瘤相关抗原(TAA)筛选策略的进展加速了生物标志物以及肿瘤亚型、诊断和治疗潜在靶分子的鉴定与表征,这可能有助于个体疾病的早期检测和诊断,并加强癌症的治疗方法。在过去几十年中,大量致力于鉴定新型靶分子的非侵入性方法主要聚焦于发现由自身抗体库或细胞毒性T淋巴细胞识别的人类肿瘤抗原,其中重组cDNA表达文库的血清学分析(SEREX)技术是最早建立的,且具有出色的灵敏度和抗原覆盖率。该方法涉及用癌症患者的血清对从新鲜肿瘤组织中提取的cDNA文库进行免疫筛选,以鉴定被IgG抗体识别的基因产物。SEREX定义的克隆可以直接测序,其表达谱也能很容易地确定,从而可以立即对抗抗原靶点进行结构定义,并随后鉴定TAA及其同源自身抗体。本综述不仅致力于概述SEREX技术及其优势、缺点以及目前可用于发现引发性肿瘤抗原的最新改进,还致力于将这些SEREX定义的肽转化为有价值的癌症特异性特征,这将有助于癌症患者诊断、预后和治疗的发展。