title: mRNA Cancer Vaccines.
abstract: 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.
authors.affiliation: CureVac AG, Paul-Ehrlich-Str. 15, 72076, Tübingen, Germany. katja.fiedler@curevac.com.
authors.forename: Katja
authors.initials: K
authors.lastname: Fiedler
authors.affiliation: CureVac AG, Paul-Ehrlich-Str. 15, 72076, Tübingen, Germany.
authors.forename: Sandra
authors.initials: S
authors.lastname: Lazzaro
authors.affiliation: CureVac AG, Paul-Ehrlich-Str. 15, 72076, Tübingen, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Lutz
authors.affiliation: CureVac AG, Paul-Ehrlich-Str. 15, 72076, Tübingen, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Rauch
authors.affiliation: CureVac AG, Paul-Ehrlich-Str. 15, 72076, Tübingen, Germany.
authors.forename: Regina
authors.initials: R
authors.lastname: Heidenreich
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D019496:Cancer Vaccines / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism / Q000637:transplantation; D015972:Gene Expression Regulation, Neoplastic; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods*; D009369:Neoplasms / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000628:therapy*; D012333:RNA, Messenger / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000637:transplantation
chemical_list: D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D012333:RNA, Messenger; D011948:Receptors, Antigen, T-Cell
keywords: Chimeric antigen receptor (CAR) T cell immunotherapy; Personalized mRNA vaccines; RNActive® vaccines; mRNA-pulsed dendritic cells