核酸适配体在肿瘤免疫治疗中的应用

核酸适配体是指通过指数富集的配体系统进化技术(systematic evolution of ligands by exponential enrichment, SELEX)技术得到的一种可以高特异性、高亲和性识别靶标物质的单链DNA或RNA,可以作为靶向性治疗的分子探针。指数富集的配体系统进化技术即SELEX技术是在体外合成一个随机序列的文库,通过4个步骤孵育、分离、回收、扩增即可获得相对应的核酸适配体。通过几十年的发展,如今SELEX技术已成为一种重要的研究手段。核酸适配体具有稳定性强、分子量小、易进行化学合成和修饰、能特异性结合包括从小分子到细胞等靶标,识别范围广等优点,被广泛应用在肿瘤领域。免疫治疗与传统的肿瘤治疗方式不同,它是增强机体自身免疫系统来达到清除体内肿瘤细胞的一种方式,已被临床证明是治疗多种癌症的有效方法,例如针对免疫检查点CTLA4和PD-L1/PD-1的抗体,临床试验取得了成功,这为肿瘤的治疗带来了新的思路方法。目前,相关的免疫治疗药物已经上市应用于临床治疗,但是通过免疫治疗获益的肿瘤患者相对较少且会产生严重的副作用。核酸适配体与免疫相结合,为肿瘤的治疗提供了一种新的研究思路。本文总结了近年来针对免疫系统筛选获得的核酸适配体及其在肿瘤免疫治疗中的应用。

The Application of Aptamers in Tumor Immunotherapy

Aptamers are single stranded DNA or RNA by SELEX (systematic evolution of ligands by exponential enrichment) strategy. They can recognize the target substance with high specificity and affinity, which can be used as a molecular probe for targeted therapy. SELEX technology is a library of random sequences synthesized in vitro. Aptamers can be obtained through four steps: incubation, separation, recovery and amplification. After decades of development, SELEX technology has become an important research method. Aptamers are widely used in the field of tumor because of their strong stability, small molecular weight, easy chemical synthesis and modification, and specificity for targets from small molecules to cells. Immunotherapy is different from traditional tumor therapy by enhancing the body's autoimmune system to eliminate tumor cells from the body. Immunotherapy has been proved to be an effective method to treat a variety of cancers. Clinical trials of antibodies against immunomodulators of CTLA4 and PD-L1/PD-1 have been successful, which has brought new ideas and methods for tumor treatment. At present, relevant immunotherapeutic drugs have been listed for clinical treatment, but relatively few tumor patients benefit from immunotherapy and will produce serious side effects. The application of aptamer in immunnotherapy provides a new strategy for the treatment of tumor. This paper summarizes the application of aptamers screened for immune system in tumor immunotherapy in recent years.