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mRNA 癌症疗法。

mRNA-based cancer therapeutics.

机构信息

Center for Nanomedicine and Department of Anaesthesiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.

Liangzhu Laboratory, Zhejiang University Medical Center, Hangzhou, China.

出版信息

Nat Rev Cancer. 2023 Aug;23(8):526-543. doi: 10.1038/s41568-023-00586-2. Epub 2023 Jun 13.

Abstract

Due to the fact that mRNA technology allows the production of diverse vaccines and treatments in a shorter time frame and with reduced expense compared to conventional approaches, there has been a surge in the use of mRNA-based therapeutics in recent years. With the aim of encoding tumour antigens for cancer vaccines, cytokines for immunotherapy, tumour suppressors to inhibit tumour development, chimeric antigen receptors for engineered T cell therapy or genome-editing proteins for gene therapy, many of these therapeutics have shown promising efficacy in preclinical studies, and some have even entered clinical trials. Given the evidence supporting the effectiveness and safety of clinically approved mRNA vaccines, coupled with growing interest in mRNA-based therapeutics, mRNA technology is poised to become one of the major pillars in cancer drug development. In this Review, we present in vitro transcribed mRNA-based therapeutics for cancer treatment, including the characteristics of the various types of synthetic mRNA, the packaging systems for efficient mRNA delivery, preclinical and clinical studies, current challenges and future prospects in the field. We anticipate the translation of promising mRNA-based treatments into clinical applications, to ultimately benefit patients.

摘要

由于 mRNA 技术相较于传统方法能够在更短的时间内以更低的成本生产出多样化的疫苗和治疗药物,近年来,基于 mRNA 的治疗药物的应用呈激增态势。为了在癌症疫苗中编码肿瘤抗原、在免疫疗法中编码细胞因子、在肿瘤抑制中抑制肿瘤发展、在基因工程 T 细胞治疗中编码嵌合抗原受体或在基因治疗中编码基因组编辑蛋白,许多此类治疗药物在临床前研究中表现出了有前景的疗效,其中一些甚至已经进入临床试验。鉴于临床批准的 mRNA 疫苗的有效性和安全性得到了证实,再加上人们对基于 mRNA 的治疗药物的兴趣日益浓厚,mRNA 技术有望成为癌症药物开发的主要支柱之一。在这篇综述中,我们介绍了用于癌症治疗的体外转录 mRNA 治疗药物,包括各种类型的合成 mRNA 的特性、高效 mRNA 递送的包装系统、临床前和临床研究、当前的挑战和该领域的未来展望。我们期待有前景的基于 mRNA 的治疗方法能够转化为临床应用,最终使患者受益。

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