核酸适配体介导的肿瘤免疫治疗研究进展

Research Progress of Aptamer-mediated Tumor Immunotherapy

肿瘤免疫治疗是一种新的肿瘤治疗方式,在临床治疗中具有重要意义和应用前景,主要包括过继性细胞免疫治疗、肿瘤疫苗和抗体肿瘤免疫治疗。抗体在肿瘤免疫治疗中应用广泛,但其价格昂贵,质量易受不同批次的影响且存在免疫原性。核酸适配体(aptamer)是一类能与靶标高特异性高亲和力结合的短的单链寡核苷酸,素有“化学抗体”之称。核酸适配体易合成且成本低,质量稳定且免疫原性低,基于这些优势近年来也被开发用于肿瘤免疫治疗。本文综述了核酸适配体在肿瘤免疫治疗中的进展,主要包括核酸适配体通过靶向免疫检查点、共刺激受体、细胞因子、递送小干扰RNA(small interfering RNA,siRNA),间接调控肿瘤免疫进程,以及将核酸适配体修饰于细胞膜上直接介导免疫细胞靶向杀伤等。核酸适配体以多种方式在肿瘤免疫治疗中发挥作用,有潜力被开发用于临床治疗。

Tumor immunotherapy is a novel strategy for cancers,which has great significance and application prospects in clinical treatment.It mainly includes adoptive cell therapy,tumor vaccines and monoclonal antibody therapy.Antibodies are widely used in tumor immunotherapy,but their price is too high,the quality is easily influenced by different batches and have immunogenicity.Aptamers,also known as"chemical antibodies",are short single-stranded oligonucleotides which bind to their targets with high specificity and affinity.Aptamers which have low immunogenicity,are synthesized at low cost and quality stability.Based on these advantages,aptamers have been developed for tumor immunotherapy in recent years which mainly includes two aspects.One is to select immune-related aptamers,and the other is to expand the application of aptamers that have been reported to tumor immunotherapy.Using immune checkpoints,co-stimulatory receptors or cytokines as targets,the aptamers can be obtained through screening.However,it is uncertain whether the aptamer has the biological function of regulating the anti-tumor immune response.Therefore,the process of screening should be improved by adding appropriate screening pressure to obtain functional aptamers that can regulate antitumor immune response.There are many aptamers which have been reported,but rarely have been investigated for further research and application.So we can further develop these aptamers for tumor immunotherapy.For example,aptamers can be coupled with siRNA or nanomaterials to indirectly regulate tumor immune processes.The modification of membrane of immune cells with aptamers confers the immune cells targeted tumor-killing effects.Aptamers play an important role in tumor immunotherapy in a variety of ways,and have great potential to be developed for clinical treatment.We need to improve the aptamer screening process to obtain aptamers that have powerful biological functions quickly and maximize the use of the aptamers that have been obtained.