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Aptamers: novelty tools for cancer biology

机译:适体:癌症生物学的新颖工具

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摘要

Although the term ‘cancer’ was still over two thousand years away of being coined, the first known cases of the disease date back to about 3000BC, in ancient Egypt. Five thousand years later, still lacking a cure, it has become one of the leading causes of death, killing over half a dozen million people yearly. So far, monoclonal antibodies are the most successful immune-therapy tools when it comes to fighting cancer. The number of clinical trials that use them has been increasing steadily during the past few years, especially since the Food and Drug Administration greenlit the use of the first immune-checkpoint blockade antibodies. However, albeit successful, this approach does come with the cost of auto-inflammatory toxicity. Taking this into account, the development of new therapeutic reagents with low toxicity becomes evident, particularly ones acting in tandem with the tools currently at our disposal. Ever since its discovery in the early nineties, aptamer technology has been used for a wide range of diagnostic and therapeutic applications. With similar properties to those of monoclonal antibodies, such as high-specificity of recognition and high-affinity binding, and the advantages of being developed using in vitro selection procedures, aptamers quickly became convenient building blocks for the generation of multifunctional constructs. In this review, we discuss the steps involved in the in vitro selection process that leads to functional aptamers - known as Systematic Evolution of Ligands by Exponential Enrichment - as well as the most recent applications of this technology in diagnostic and treatment of oncological illnesses. Moreover, we also suggest ways to improve such use.
机译:尽管“癌症”一词距离创造尚有两千多年的历史,但该疾病的首例已知病例可追溯到古埃及,大约在公元前3000年。五千年后,仍然没有治愈方法,它已成为主要的死亡原因之一,每年造成六十万人死亡。迄今为止,单克隆抗体是抗击癌症最成功的免疫疗法工具。在过去的几年中,使用它们的临床试验数量一直在稳定增长,尤其是自从食品药品监督管理局批准了首个免疫检查点封锁抗体的绿色使用以来。然而,尽管成功,但这种方法的确伴随了自身炎症毒性的代价。考虑到这一点,开发出低毒性的新型治疗剂变得尤为明显,特别是那些与我们目前使用的工具协同作用的治疗剂。自从90年代初发现以来,适体技术已被广泛用于诊断和治疗应用。具有与单克隆抗体相似的特性,例如识别的高特异性和高亲和力,以及使用体外选择程序开发的优势,适体​​迅速成为方便的构建基块,用于生成多功能构建体。在这篇综述中,我们讨论了导致功能性适体(称为通过指数富集的配体的系统进化)的体外选择过程中涉及的步骤,以及该技术在肿瘤疾病的诊断和治疗中的最新应用。此外,我们还建议了改善此类使用的方法。

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