Hinz Thomas, Kallen Kajo, Britten Cedrik M, Flamion Bruno, Granzer Ulrich, Hoos Axel, Huber Christoph, Khleif Samir, Kreiter Sebastian, Rammensee Hans-Georg, Sahin Ugur, Singh-Jasuja Harpreet, Türeci Özlem, Kalinke Ulrich
Section for Therapeutic Vaccines, Division for Immunology, Paul-Ehrlich-Institut, Paul-Ehrlich-Str. 51-59, 63225, Langen, Germany.
Kallen Consulting, Köln/Frechen, Germany.
Methods Mol Biol. 2017;1499:203-222. doi: 10.1007/978-1-4939-6481-9_13.
A variety of different mRNA-based drugs are currently in development. This became possible, since major breakthroughs in RNA research during the last decades allowed impressive improvements of translation, stability and delivery of mRNA. This article focuses on antigen-encoding RNA-based vaccines that are either directed against tumors or pathogens. mRNA-encoded vaccines are developed both for preventive or therapeutic purposes. Most mRNA-based vaccines are directly administered to patients. Alternatively, primary autologous cells from cancer patients are modified ex vivo by the use of mRNA and then are adoptively transferred to patients. In the EU no regulatory guidelines presently exist that specifically address mRNA-based vaccines. The existing regulatory framework, however, clearly defines that mRNA-based vaccines in most cases have to be centrally approved. Interestingly, depending on whether RNA-based vaccines are directed against tumors or infectious disease, they are formally considered gene therapy products or not, respectively. Besides an overview on the current clinical use of mRNA vaccines in various therapeutic areas a detailed discussion of the current regulatory situation is provided and regulatory perspectives are discussed.
目前有多种不同的基于mRNA的药物正在研发中。这之所以成为可能，是因为过去几十年RNA研究取得了重大突破，使得mRNA的翻译、稳定性和递送方面有了显著改进。本文重点关注针对肿瘤或病原体的基于RNA编码抗原的疫苗。基于mRNA的疫苗既用于预防目的，也用于治疗目的。大多数基于mRNA的疫苗直接给患者施用。或者，癌症患者的原代自体细胞通过使用mRNA在体外进行改造，然后回输到患者体内。在欧盟，目前不存在专门针对基于mRNA的疫苗的监管指南。然而，现有的监管框架明确规定，在大多数情况下，基于mRNA的疫苗必须获得集中批准。有趣的是，根据基于RNA的疫苗是针对肿瘤还是传染病，它们分别被正式视为基因治疗产品或非基因治疗产品。除了概述mRNA疫苗在各个治疗领域的当前临床应用外，还提供了对当前监管情况的详细讨论，并探讨了监管前景。
