Mathieu Morgan G, Linley Adam J, Reeder Stephen P, Badoual Cécile, Tartour Eric, Rees Robert C, McArdle Stéphanie E B
The John van Geest Cancer Research Centre, School of Science and Technology, Nottingham Trent University, Clifton Lane, NG11 8NS Nottingham, United Kingdom.
Cancer Immun. 2010 Jan 11;10:2.
The search for novel tumour antigens that are either uniquely expressed or over-expressed in a wide variety of tumours is still ongoing. Because of their expression in a broad spectrum of cancers and limited expression in normal tissues, cancer/testis antigens are considered to be potentially reliable targets for immunotherapy of cancer in general. The helicase antigen HAGE has been identified as a cancer/testis antigen. However, little is known about its expression in normal and cancer tissues. Using a newly developed antibody against HAGE, specific staining of its expression by immunohistochemistry was validated and optimised on murine tumours transfected to express the HAGE protein. The antibody was subsequently used to determine HAGE expression in normal human and cancer tissue microarrays. HAGE protein expression was confirmed in 75% (12/16) of carcinomas as compared to normal tissues, which either did not express HAGE at all or expressed HAGE at very low levels with the exception of testis. Interestingly, discrepancies were also found between mRNA analysis by real time quantitative PCR (RT-qPCR) and protein analysis by immunohistochemistry, emphasising the need to validate the expression of cancer/testis antigens at the protein level prior to the development of new vaccine strategies. HAGE is therefore proposed to be a valid candidate for designing a broad spectrum vaccine against cancer.
寻找在多种肿瘤中独特表达或过度表达的新型肿瘤抗原的工作仍在进行中。由于癌症/睾丸抗原在广泛的癌症中表达,而在正常组织中表达有限,总体上它们被认为是癌症免疫治疗潜在的可靠靶点。解旋酶抗原HAGE已被鉴定为一种癌症/睾丸抗原。然而,关于其在正常组织和癌组织中的表达情况却知之甚少。使用新开发的针对HAGE的抗体,通过免疫组织化学对其表达的特异性染色在转染以表达HAGE蛋白的鼠肿瘤上得到验证和优化。随后该抗体被用于确定HAGE在正常人体组织和癌组织微阵列中的表达。与正常组织相比,在75%(12/16)的癌组织中证实了HAGE蛋白表达,正常组织除睾丸外要么根本不表达HAGE,要么表达水平极低。有趣的是,实时定量PCR(RT-qPCR)的mRNA分析与免疫组织化学的蛋白质分析之间也存在差异,这强调了在开发新疫苗策略之前在蛋白质水平验证癌症/睾丸抗原表达的必要性。因此,HAGE被认为是设计广谱抗癌疫苗的有效候选物。