Morita Yoshihiro, Leslie Macall, Kameyama Hiroyasu, Volk David E, Tanaka Takemi
Stephenson Cancer Center, University of Oklahoma Health Sciences Center, 975 NE 10th, BRC-W, Rm 1415, Oklahoma City, OK 73104, USA.
McGovern Medical School, Institute of Molecular Medicine, University of Texas Health Science Center at Houston, 1825 Hermann Pressler, Houston, TX 77030, USA.
Cancers (Basel). 2018 Mar 19;10(3):80. doi: 10.3390/cancers10030080.
Aptamer-related technologies represent a revolutionary advancement in the capacity to rapidly develop new classes of targeting ligands. Structurally distinct RNA and DNA oligonucleotides, aptamers mimic small, protein-binding molecules and exhibit high binding affinity and selectivity. Although their molecular weight is relatively small-approximately one-tenth that of monoclonal antibodies-their complex tertiary folded structures create sufficient recognition surface area for tight interaction with target molecules. Additionally, unlike antibodies, aptamers can be readily chemically synthesized and modified. In addition, aptamers' long storage period and low immunogenicity are favorable properties for clinical utility. Due to their flexibility of chemical modification, aptamers are conjugated to other chemical entities including chemotherapeutic agents, siRNA, nanoparticles, and solid phase surfaces for therapeutic and diagnostic applications. However, as relatively small sized oligonucleotides, aptamers present several challenges for successful clinical translation. Their short plasma half-lives due to nuclease degradation and rapid renal excretion necessitate further structural modification of aptamers for clinical application. Since the US Food and Drug Administration (FDA) approval of the first aptamer drug, Macugen (pegaptanib), which treats wet-age-related macular degeneration, several aptamer therapeutics for oncology have followed and shown promise in pre-clinical models as well as clinical trials. This review discusses the advantages and challenges of aptamers and introduces therapeutic aptamers under investigation and in clinical trials for cancer treatments.
适体相关技术代表了在快速开发新型靶向配体能力方面的一项革命性进展。适体是结构独特的RNA和DNA寡核苷酸，模拟小分子蛋白质结合分子，具有高结合亲和力和选择性。尽管它们的分子量相对较小——约为单克隆抗体的十分之一——但其复杂的三级折叠结构为与靶分子紧密相互作用创造了足够的识别表面积。此外，与抗体不同，适体可以很容易地进行化学合成和修饰。另外，适体的长储存期和低免疫原性是有利于临床应用的特性。由于其化学修饰的灵活性，适体可与包括化疗药物、小干扰RNA、纳米颗粒和固相表面在内的其他化学实体偶联，用于治疗和诊断应用。然而，作为相对较小的寡核苷酸，适体在成功的临床转化方面面临几个挑战。由于核酸酶降解和肾脏快速排泄导致其血浆半衰期较短，因此需要对适体进行进一步的结构修饰以用于临床应用。自美国食品药品监督管理局（FDA）批准首款适体药物Macugen（pegaptanib，用于治疗湿性年龄相关性黄斑变性）以来，已有几种用于肿瘤学的适体疗法相继出现，并在临床前模型和临床试验中显示出前景。本文综述讨论了适体的优势和挑战，并介绍了正在研究的以及用于癌症治疗的临床试验中的治疗性适体。
