title: mRNA: From a chemical blueprint for protein production to an off-the-shelf therapeutic.
abstract: Two decades ago, mRNA became the focus of research in molecular medicine and was proposed as an active pharmaceutical ingredient for the therapy of cancer. In this regard, mRNA has been mainly used for ex vivo modification of antigen-presenting cells (APCs), such as dendritic cells (DCs). This vaccination strategy has proven to be safe, well tolerated and capable of inducing tumor antigen-specific immune responses. Recently, the direct application of mRNA for in situ modification of APCs, hence immunization was shown to be feasible and at least as effective as DC-based immunization in pre-clinical models. It is believed that application of mRNA as an off-the-shelf vaccine represents an important step in the development of future cancer immunotherapeutic strategies. Here, we will discuss the use of ex vivo mRNA-modified DCs and "naked mRNA" for cancer immunotherapy focusing on parameters such as the employed DC subtype, DC activation stimulus and route of immunization. In addition, we will provide an overview on the clinical trials published so far, trying to link their outcome to the aforementioned parameters.
authors.affiliation: Laboratory of Molecular and Cellular Therapy; Department of Immunology-Physiology; Medical School of the "Vrije Universiteit Brussel"; Jette, Belgium.
authors.forename: Sandra
authors.initials: S
authors.lastname: Van Lint
authors.forename: Carlo
authors.initials: C
authors.lastname: Heirman
authors.forename: Kris
authors.initials: K
authors.lastname: Thielemans
authors.forename: Karine
authors.initials: K
authors.lastname: Breckpot
mesh_terms: D001688:Biological Products / Q000378:metabolism*; D019496:Cancer Vaccines / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D055808:Drug Discovery / Q000639:trends; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D009369:Neoplasms / Q000628:therapy; D012333:RNA, Messenger / Q000378:metabolism*
chemical_list: D001688:Biological Products; D019496:Cancer Vaccines; D012333:RNA, Messenger
keywords: cancer; dendritic cell; immunotherapy; mRNA