Nagano Kazuya
Laboaratoy of Toxicology and Safety Sciences, Graduate School of Pharmaceutical Sciences, Osaka University.
Yakugaku Zasshi. 2016;136(2):145-9. doi: 10.1248/yakushi.15-00226-1.
Disease proteomics that systemically analyzes and identifies differentially expressed proteins between healthy and diseased samples is a potentially useful approach for obtaining target proteins for drug development. To date, however, very few target proteins have been identified from this field. A key issue that remains to be resolved is how to correctly identify target proteins from a number of potential candidates. To circumvent this problem, we have developed "antibody proteomics technology" in which a single chain Fv phage antibody library is utilized for proteome analysis. Here, we describe the application of this technology by primarily focusing on Eph receptor A10 (EphA10), a novel breast cancer-related protein that is a promising target for antibody drugs. To establish an effective and safe targeted cancer therapy, it is important that the target is specifically expressed in cancer tissues. Therefore, we attempted to analyze the EphA10 expression profiles. Tissue microarray analysis showed that EphA10 was expressed in all subtypes of breast cancer containing triple negative breast cancer cases. On the other hand, EphA10 was only expressed in testis tissue among 36 kinds of normal tissues. Thus, EphA10 could be a highly cancer-specific protein, making it a promising target for female breast cancer patients. Finally, we examined the anti-tumor effect by anti-EphA10 antibody, aiming for the development of a novel EphA10 targeting therapy. Administration of the antibody showed that tumor volumes were significantly inhibited. Our results suggest that targeting EphA10 in breast cancer cases might be a promising new form of therapy.
疾病蛋白质组学系统地分析和鉴定健康样本与患病样本之间差异表达的蛋白质，是一种潜在有用的方法，可用于获取药物开发的靶蛋白。然而，迄今为止，从该领域鉴定出的靶蛋白非常少。一个有待解决的关键问题是如何从众多潜在候选物中正确鉴定靶蛋白。为了规避这个问题，我们开发了“抗体蛋白质组学技术”，其中利用单链Fv噬菌体抗体库进行蛋白质组分析。在此，我们主要聚焦于Eph受体A10（EphA10）来描述这项技术的应用，EphA10是一种与乳腺癌相关的新型蛋白质，是抗体药物的一个有前景的靶点。为了建立有效且安全的靶向癌症治疗方法，靶点在癌组织中特异性表达很重要。因此，我们试图分析EphA10的表达谱。组织微阵列分析表明，EphA10在包括三阴性乳腺癌病例在内的所有乳腺癌亚型中均有表达。另一方面，在36种正常组织中，EphA10仅在睾丸组织中表达。因此，EphA10可能是一种高度癌症特异性的蛋白质，使其成为女性乳腺癌患者的一个有前景的靶点。最后，我们检测了抗EphA10抗体的抗肿瘤效果，旨在开发一种新型的靶向EphA10的治疗方法。抗体给药显示肿瘤体积受到显著抑制。我们的结果表明，针对乳腺癌病例靶向EphA10可能是一种有前景的新治疗形式。
