Fiedler Katja, Lazzaro Sandra, Lutz Johannes, Rauch Susanne, Heidenreich Regina
CureVac AG, Paul-Ehrlich-Str. 15, 72076, Tübingen, Germany.
Recent Results Cancer Res. 2016;209:61-85. doi: 10.1007/978-3-319-42934-2_5.
mRNA cancer vaccines are a relatively new class of vaccines, which combine the potential of mRNA to encode for almost any protein with an excellent safety profile and a flexible production process. The most straightforward use of mRNA vaccines in oncologic settings is the immunization of patients with mRNA vaccines encoding tumor-associated antigens (TAAs). This is exemplified by the RNActive technology, which induces balanced humoral and cellular immune responses in animal models and is currently evaluated in several clinical trials for oncologic indications. A second application of mRNA vaccines is the production of personalized vaccines. This is possible because mRNA vaccines are produced by a generic process, which can be used to quickly produce mRNA vaccines targeting patient-specific neoantigens that are identified by analyzing the tumor exome. Apart from being used directly to vaccinate patients, mRNAs can also be used in cellular therapies to transfect patient-derived cells in vitro and infuse the manipulated cells back into the patient. One such application is the transfection of patient-derived dendritic cells (DCs) with mRNAs encoding TAAs, which leads to the presentation of TAA-derived peptides on the DCs and an activation of antigen-specific T cells in vivo. A second application is the transfection of patient-derived T cells with mRNAs encoding chimeric antigen receptors, which allows the T cells to directly recognize a specific antigen expressed on the tumor. In this chapter, we will review preclinical and clinical data for the different approaches.
信使核糖核酸癌症疫苗是一类相对较新的疫苗，它将信使核糖核酸编码几乎任何蛋白质的潜力与出色的安全性和灵活的生产工艺结合在一起。信使核糖核酸疫苗在肿瘤学环境中最直接的用途是用编码肿瘤相关抗原（TAAs）的信使核糖核酸疫苗对患者进行免疫接种。RNActive技术就是一个例子，它在动物模型中诱导平衡的体液免疫和细胞免疫反应，目前正在多项肿瘤学适应症的临床试验中进行评估。信使核糖核酸疫苗的第二个应用是生产个性化疫苗。这是可行的，因为信使核糖核酸疫苗是通过通用工艺生产的，该工艺可用于快速生产针对通过分析肿瘤外显子组确定的患者特异性新抗原的信使核糖核酸疫苗。除了直接用于给患者接种疫苗外，信使核糖核酸还可用于细胞疗法，在体外转染患者来源的细胞，并将经过处理的细胞重新注入患者体内。一种这样的应用是用编码肿瘤相关抗原的信使核糖核酸转染患者来源的树突状细胞（DCs），这会导致肿瘤相关抗原衍生的肽在树突状细胞上呈递，并在体内激活抗原特异性T细胞。第二个应用是用编码嵌合抗原受体的信使核糖核酸转染患者来源的T细胞，这使得T细胞能够直接识别肿瘤上表达的特定抗原。在本章中，我们将回顾不同方法的临床前和临床数据。
