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招募体外转录 mRNA 用于肿瘤免疫治疗:当前格局的当代评估

英文原题:Recruiting In Vitro Transcribed mRNA against Cancer Immunotherapy: A Contemporary Appraisal of the Current Landscape.

PubMed 2023/11/16(内容时间) Curr Issues Mol Biol Q2 · IF 4.1(JCR 2025)

研究概要

目前有超过 100 种创新的体外转录(IVT)mRNA 正在开展临床试验,预计在不久的将来会对医药市场产生重大影响。

中文摘要

目前有100多种创新的体外转录(IVT)mRNA正在开展临床试验,预计不久将在药物市场产生重大影响。其基本原理是:IVT-mRNA成功进入细胞后,可被翻译成具有治疗或预防作用的蛋白质。与此同时,癌症免疫治疗采用多种策略动员免疫系统对抗癌症。因此,本综述讨论并分析IVT-mRNA的基本原理及其在癌症免疫治疗中的应用。具体而言,文章重点介绍mRNA疫苗开发、新抗原利用及嵌合抗原受体(CAR)T细胞疗法,并展示其临床应用及开发下一代免疫疗法的在研试验。此外,研究探讨CAR免疫疗法与IVT-mRNA联合的协同潜力,并介绍本研究团队一项新型专利递送方法:利用蛋白转导结构域(PTD)技术,将编码目标CAR的IVT-mRNA转导至NK-92NK 细胞,显示其可能提高CAR-NK细胞效力、效率及生物能量学特征。尽管IVT-mRNA技术为癌症免疫治疗带来令人振奋的进展,仍须考虑安全性、毒性和递送等挑战与局限。本文全面探讨IVT-mRNA技术及其在癌症治疗中的应用,为这一不断演变领域的机遇和挑战提供见解,并为未来进展奠定基础。

展开英文摘要原文

Over 100 innovative in vitro transcribed (IVT)-mRNAs are presently undergoing clinical trials, with a projected substantial impact on the pharmaceutical market in the near future. he idea behind this is that after the successful cellular internalization of IVT-mRNAs, they are subsequently translated into proteins with therapeutic or prophylactic relevance. Simultaneously, cancer immunotherapy employs diverse strategies to mobilize the immune system in the battle against cancer. Therefore, in this review, the fundamental principles of IVT-mRNA to its recruitment in cancer immunotherapy, are discussed and analyzed. More specifically, this review paper focuses on the development of mRNA vaccines, the exploitation of neoantigens, as well as Chimeric Antigen Receptor (CAR) T-Cells, showcasing their clinical applications and the ongoing trials for the development of next-generation immunotherapeutics. Furthermore, this study investigates the synergistic potential of combining the CAR immunotherapy and the IVT-mRNAs by introducing our research group novel, patented delivery method that utilizes the Protein Transduction Domain (PTD) technology to transduce the IVT-mRNAs encoding the CAR of interest into the Natural Killer (NK)-92 cells, highlighting the potential for enhancing the CAR NK cell potency, efficiency, and bioenergetics. While IVT-mRNA technology brings exciting progress to cancer immunotherapy, several challenges and limitations must be acknowledged, such as safety, toxicity, and delivery issues. This comprehensive exploration of IVT-mRNA technology, in line with its applications in cancer therapeutics, offers valuable insights into the opportunities and challenges in the evolving landscape of cancer immunotherapy, setting the stage for future advancements in the field.

论文信息

作者
Miliotou AN、Georgiou-Siafis SK、Ntenti C、Pappas IS、Papadopoulou LC
单位
Laboratory of Pharmacology, School of Pharmacy, Faculty of Health Sciences, Aristotle University of Thessaloniki, 54124 Thessaloniki, Macedonia, Greece.Greece
文献类型
综述
期刊
Current issues in molecular biology2023 Nov 16
原文标识
PubMed 37998753 · DOI 10.3390/cimb45110576