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治疗范式从 Covid-19 向肿瘤学的转变:mRNA 疫苗

英文原题:The paradigm shift in treatment from Covid-19 to oncology with mRNA vaccines.

查看英文原题

The paradigm shift in treatment from Covid-19 to oncology with mRNA vaccines.

PubMed 2022/05/05(内容时间) Cancer Treat Rev Q1 · IF 10.6(JCR 2025)

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中文摘要

mRNA疫苗在过去十年中作为一种开发新型疗法的多功能工具而日益受到欢迎。近期冠状病毒病(COVID-19)mRNA疫苗的成功释放了mRNA技术作为强大治疗平台的潜力。在这篇综述中,我们评估了关于各种类型癌症疫苗、可用于疫苗递送的新型平台、基于RNA的疗法的最新进展以及mRNA疫苗在各种癌症适应症中不断演变的作用的文献,并提出了治疗患者的未来策略。文献表明,尽管mRNA疫苗的开发面临多方面挑战,但RNA在临床前和临床研究中展现出的有前景且持久的疗效值得考虑。mRNA转染DC疫苗的引入是一种在癌症疫苗开发中引起关注的方法,因为它能够规避DC分离、体外培养和再输注的必要性。选择合适的靶抗原仍然是癌症疫苗开发的主要挑战之一。mRNA平台的快速开发和大规模生产使得个性化疫苗(mRNA 4157、mRNA 4650和RO7198457)和四价疫苗(BNT111和mRNA-5671)的开发成为可能。

此外,mRNA疫苗与检查点调节剂及其他逆转免疫抑制的新型药物联合使用显示出前景,然而需要进一步研究以发现哪些组合最有效以及每种成分的最佳给药方案。每种递送途径(皮内、皮下、瘤内、结内、鼻内、静脉内)都有其自身需要克服的一系列挑战,而这些挑战将决定最佳的递送方法。换言之,在开发疫苗设计时,其根本动机应是递送途径与形式的合理结合。探索各种给药途径和递送途径系统促进了 mRNA 疫苗的发展。

展开英文摘要原文

mRNA vaccines have gained popularity over the last decade as a versatile tool for developing novel therapeutics. The recent success of coronavirus disease (COVID-19) mRNA vaccine has unlocked the potential of mRNA technology as a powerful therapeutic platform. In this review, we apprise the literature on the various types of cancer vaccines, the novel platforms available for delivery of the vaccines, the recent progress in the RNA-based therapies and the evolving role of mRNA vaccines for various cancer indications, along with a future strategy to treat the patients.

Literature reveals that despite multifaceted challenges in the development of mRNA vaccines, the promising and durable efficacy of the RNA in pre-clinical and clinical studies deserves consideration. The introduction of mRNA-transfected DC vaccine is an approach that has gained interest for cancer vaccine development due to its ability to circumvent the necessity of DC isolation, ex vivo cultivation and re-infusion.

The selection of appropriate antigen of interest remains one of the major challenges for cancer vaccine development. The rapid development and large-scale production of mRNA platform has enabled for the development of both personalized vaccines (mRNA 4157, mRNA 4650 and RO7198457) and tetravalent vaccines (BNT111 and mRNA-5671).

In addition, mRNA vaccines combined with checkpoint modulators and other novel medications that reverse immunosuppression show promise, however further research is needed to discover which combinations are most successful and the best dosing schedule for each component.

Each delivery route (intradermal, subcutaneous, intra tumoral, intranodal, intranasal, intravenous) has its own set of challenges to overcome, and these challenges will decide the best delivery method. In other words, while developing a vaccine design, the underlying motivation should be a reasonable combination of delivery route and format. Exploring various administration routes and delivery route systems has boosted the development of mRNA vaccines.

论文信息

作者
Wei J、Hui AM
第一作者单位
Shanghai Fosun Pharmaceutical Industrial Development, Co., Ltd., 1289 Yishan Road, Shanghai 200233, China; Fosun Pharma USA Inc, 91 Hartwell Avenue, Suite 305, Lexington, MA 02421, USA.China
通讯作者单位
Shanghai Fosun Pharmaceutical Industrial Development, Co., Ltd., 1289 Yishan Road, Shanghai 200233, China; Fosun Pharma USA Inc, 91 Hartwell Avenue, Suite 305, Lexington, MA 02421, USA. Electronic address: aimin.hui@fosunpharma.com.China
文献类型
综述
期刊
Cancer treatment reviews2022 Jun
原文标识
PubMed 35576777 · DOI 10.1016/j.ctrv.2022.102405