中文摘要：受体酪氨酸激酶(RTKs)是一个完整的膜传感器，控制细胞分化、增殖和移动，并使细胞和环境之间快速通信。目前已知的20个RTK亚家族中，Eph受体是最大的类群。Eph受体与相应的ephrin配体一起调节多种生理过程，包括轴突引导、骨重塑、免疫细胞发育和运输。Eph信号通路的反常与癌症和其他增生性疾病有关，且因RTKs在癌症发展中发挥关键作用，这些分子在恶性肿瘤中的特定靶向提供了一个有前途的治疗方法。靶向RTKs的单克隆抗体由于其相对较高的靶标特异性和较低的脱靶结合率，是一种潜在的有吸引力的药物开发模式。因此，在自身体内环境中产生靶向RTKs抗体的新技术，可促进抗体治疗的临床前和临床发展。本研究小组最近报道了一种平台发现方法-噬菌体展示可获得性重组靶向抗体筛选(SPARTA)。它是一种新颖而稳健的逐步筛选方法，结合了针对已知肿瘤靶点的人类天然重组抗体库的体外筛选特性和基于预富集抗体库肿瘤归巢能力的体内筛选特性。这种方法独特地克服了一些限制人单克隆抗体快速产生的问题，其可以迅速转化为医学应用。
外文摘要：Receptor tyrosine kinases (RTKs) are integral membrane sensors that govern cell differentiation, proliferation and mobility, and enable rapid communication between cells and their environment. Of the 20 RTK subfamilies currently known, Eph receptors are the largest group. Together with their corresponding ephrin ligands, Eph receptors regulate a diverse array of physiologic processes including axonal guidance, bone remodeling, and immune cell development and trafficking. Deregulation of Eph signaling pathways is linked to cancer and other proliferative diseases and, because RTKs play critical roles in cancer development, the specific targeting of these molecules in malignancies provides a promising treatment approach. Monoclonal antibodies targeting RTKs represent a potentially attractive modality for pharmaceutical development due to their relatively high target specificity and low off-target binding rates. Therefore, new technologies to generate antibodies able to target RTKs in their native in vivo context are likely to facilitate pre-clinical and clinical development of antibody-based therapies. Our group has recently reported a platform discovery methodology termed Selection of Phage-displayed Accessible Recombinant Targeted Antibodies (SPARTA). SPARTA is a novel and robust stepwise method, which combines the attributes of in vitro screenings of a naive human recombinant antibody library against known tumor targets with those features of in vivo selections based on tumor-homing capabilities of a pre-enriched antibody pool. This unique approach overcomes several rate-limiting challenges to generate human monoclonal antibodies amenable to rapid translation into medical applications.
作者：Tang, FHF；Davis, D；Arap, W；Pasqualini, R；Staquicini, FI；AF Tang, Fenny H. F.；Davis, Deodate；Arap, Wadih；Pasqualini, Renata；Staquicini, Fernanda I.
作者单位：Rutgers Canc Inst New Jersey；Rutgers New Jersey Med Sch
期刊名称：图书章节
期刊影响因子：0.0
出版年份：2020
出版刊次：147
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