Dörrie Jan, Schaft Niels, Schuler Gerold, Schuler-Thurner Beatrice
Department of Dermatology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Hartmannstraße 14, 91052 Erlangen, Germany.
Pharmaceutics. 2020 Jan 23;12(2):92. doi: 10.3390/pharmaceutics12020092.
Over the last two decades, dendritic cell (DC) vaccination has been studied extensively as active immunotherapy in cancer treatment and has been proven safe in all clinical trials both with respect to short and long-term side effects. For antigen-loading of dendritic cells (DCs) one method is to introduce mRNA coding for the desired antigens. To target the whole antigenic repertoire of a tumor, even the total tumor mRNA of a macrodissected biopsy sample can be used. To date, reports have been published on a total of 781 patients suffering from different tumor entities and HIV-infection, who have been treated with DCs loaded with mRNA. The majority of those were melanoma patients, followed by HIV-infected patients, but leukemias, brain tumors, prostate cancer, renal cell carcinomas, pancreatic cancers and several others have also been treated. Next to antigen-loading, mRNA-electroporation allows a purposeful manipulation of the DCs' phenotype and function to enhance their immunogenicity. In this review, we intend to give a comprehensive summary of what has been published regarding clinical testing of ex vivo generated mRNA-transfected DCs, with respect to safety and risk/benefit evaluations, choice of tumor antigens and RNA-source, and the design of better DCs for vaccination by transfection of mRNA-encoded functional proteins.
在过去二十年中，树突状细胞（DC）疫苗接种作为癌症治疗中的主动免疫疗法得到了广泛研究，并且在所有临床试验中均已证明，无论短期还是长期副作用，其都是安全的。对于树突状细胞（DC）的抗原加载，一种方法是引入编码所需抗原的mRNA。为了靶向肿瘤的整个抗原库，甚至可以使用大切片活检样本的总肿瘤mRNA。迄今为止，已经发表了关于781例患有不同肿瘤实体和HIV感染的患者的报告，这些患者接受了负载mRNA的DC治疗。其中大多数是黑色素瘤患者，其次是HIV感染患者，但白血病、脑肿瘤、前列腺癌、肾细胞癌、胰腺癌和其他几种癌症也接受了治疗。除了抗原加载外，mRNA电穿孔还可以有目的地操纵DC的表型和功能，以增强其免疫原性。在本综述中，我们打算全面总结关于体外产生的mRNA转染DC的临床试验已发表的内容，涉及安全性和风险/效益评估、肿瘤抗原和RNA来源的选择，以及通过转染mRNA编码的功能蛋白设计更好的DC用于疫苗接种。
