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新兴的癌症特异性治疗性适配体。

Emerging cancer-specific therapeutic aptamers.

作者信息

Yoon Sorah, Rossi John J

机构信息

aDepartment of Molecular and Cellular Biology bIrell and Manella Graduate School of Biological Sciences, Beckman Research Institute of City of Hope, Duarte, California, USA.

出版信息

Curr Opin Oncol. 2017 Sep;29(5):366-374. doi: 10.1097/CCO.0000000000000389.

Abstract

PURPOSE OF REVIEW

We will describe recently discovered smart aptamers with tumor specificity, with an emphasis on targeted delivery of novel therapeutic molecules, cancer-specific biomarkers, and immunotherapy.

RECENT FINDINGS

The development of cancer-specific aptamers has facilitated targeted delivery of potent therapeutic molecules to cancer cells without harming nontumoral cells. This specificity also makes it possible to discover novel cancer biomarkers. Furthermore, alternative immune-checkpoint blockade aptamers have been developed for combinational immunotherapy.

SUMMARY

Aptamers selected against cancer cells show cancer specificity, which has great potential for targeting. First, functionalizing targeted aptamers with therapeutic molecule payloads (e.g., small activating RNAs, antimitotic drugs, therapeutic antibodies, and peptides) facilitates successful delivery into cancer cells. This approach greatly improves the therapeutic index by minimizing side-effects in nontumoral cells. Second, cancer-specific proteins have been identified as cancer biomarkers through in-vitro and in-vivo selection, aptamer pull-down assays, and mass spectrometry. These newly discovered biomarkers improve therapeutic intervention and diagnostic specificity. In addition, the development of alternative immune-checkpoint blockade aptamers is suggested for use in combinational immunotherapeutic with current immune blockade regimens, to reduce the resistance and exhaustion of T cells in clinical trials. VIDEO ABSTRACT: http://links.lww.com/COON/A21.

摘要

综述目的

我们将描述最近发现的具有肿瘤特异性的智能适配体,重点是新型治疗分子、癌症特异性生物标志物和免疫疗法的靶向递送。

最新发现

癌症特异性适配体的开发有助于将强效治疗分子靶向递送至癌细胞,而不损害非肿瘤细胞。这种特异性还使得发现新型癌症生物标志物成为可能。此外,已开发出替代免疫检查点阻断适配体用于联合免疫治疗。

总结

针对癌细胞筛选出的适配体具有癌症特异性,具有巨大的靶向潜力。首先,用治疗分子载荷(如小激活RNA、抗有丝分裂药物、治疗性抗体和肽)对靶向适配体进行功能化,有助于成功递送至癌细胞。这种方法通过将非肿瘤细胞中的副作用降至最低,大大提高了治疗指数。其次,通过体外和体内筛选、适配体下拉分析和质谱分析,已将癌症特异性蛋白鉴定为癌症生物标志物。这些新发现的生物标志物改善了治疗干预和诊断特异性。此外,建议开发替代免疫检查点阻断适配体,用于与当前免疫阻断方案联合免疫治疗,以降低临床试验中T细胞的耐药性和耗竭。视频摘要:http://links.lww.com/COON/A21

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/765c/5706452/41d087ec715c/nihms920335f1.jpg

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