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Aptamers: A New Technological Platform in Cancer Immunotherapy

机译:适体:癌症免疫治疗的新技术平台

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摘要

The renaissance of cancer immunotherapy is, nowadays, a reality. In the near future, it will be very likely among the first-line treatments for cancer patients. There are several different approaches to modulate the immune system to fight against tumor maladies but, so far, monoclonal antibodies may currently be the most successful immuno-tools used to that end. The number of ongoing clinical trials with monoclonal antibodies has been increasing exponentially over the last few years upon the Food and Drug Administration (FDA) approval of the first immune-checkpoint blockade antibodies. In spite of the proved antitumor effect of these reagents, the unleashing of the immune system to fight cancer cells has a cost, namely auto-inflammatory toxicity. Additionally, only a small fraction of all patients treated with immune-checkpoint antibodies have a clinical benefit. Taking into account all this, it is urgent new therapeutic reagents are developed with a contained toxicity that could facilitate the combination of different immune-modulating pathways to broaden the antitumor effect in most cancer patients. Based on preclinical data, oligonucleotide aptamers could fulfill this need. Aptamers have not only been successfully used as antagonists of immune-checkpoint receptors, but also as agonists of immunostimulatory receptors in cancer immunotherapy. The simplicity of aptamers to be engineered for the specific delivery of different types of cargos to tumor cells and immune cells so as to harvest an efficient antitumor immune response gives aptamers a significant advantage over antibodies. In this review all of the recent applications of aptamers in cancer immunotherapy will be described.
机译:如今,癌症免疫疗法的复兴已经成为现实。在不久的将来,这将非常可能成为癌症患者的一线治疗药物。有几种不同的方法可调节免疫系统以对抗肿瘤病,但到目前为止,单克隆抗体可能是目前用于该目的最成功的免疫工具。在食品和药物管理局(FDA)批准了首个免疫检查点封锁抗体后,最近几年进行的单克隆抗体临床试验的数量呈指数增长。尽管已证明这些试剂具有抗肿瘤作用,但释放免疫系统来对抗癌细胞却要付出代价,即自身炎症毒性。另外,用免疫检查点抗体治疗的所有患者中只有一小部分具有临床益处。考虑到所有这些,迫切需要开发出一种新的治疗试剂,该试剂具有一定的毒性,可以促进不同免疫调节途径的结合,从而扩大大多数癌症患者的抗肿瘤作用。根据临床前数据,寡核苷酸适体可以满足这一需求。适体不仅已成功地用作免疫检查点受体的拮抗剂,而且已成功地用作癌症免疫疗法中免疫刺激受体的激动剂。为将不同类型的货物特异性递送至肿瘤细胞和免疫细胞而进行工程改造的适体的简单性,以便收获有效的抗肿瘤免疫应答,使适体具有优于抗体的显着优势。在这篇综述中,将描述适体在癌症免疫治疗中的所有最新应用。

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