title: Translating nanoparticulate-personalized cancer vaccines into clinical applications: case study with RNA-lipoplexes for the treatment of melanoma.
abstract: The development of nucleic acid based vaccines against cancer has gained considerable momentum through the advancement of modern sequencing technologies and on novel RNA-based synthetic drug formats, which can be readily adapted following identification of every patient's tumor-specific mutations. Furthermore, affordable and individual 'on demand' production of molecularly optimized vaccines should allow their application in large groups of patients. This has resulted in the therapeutic concept of an active personalized cancer vaccine, which has been brought into clinical testing. Successful trials have been performed by intranodal administration of sterile isotonic solutions of synthetic RNA vaccines. The second generation of RNA vaccines which is currently being developed encompasses intravenously injectable RNA nanoparticle formulations (lipoplexes), made up from lipid excipients, denoted RNA(LIP). A first product that has made its way from bench to bedside is a therapeutic vaccine for intravenous administration based on a fixed set of four RNA lipoplex drug products, each encoding for one shared tumor antigen (Lipoplex Melanoma RNA Immunotherapy, 'Lipo-MERIT'). This article describes the steps for translating these novel RNA nanomedicines into clinical trials.
authors.affiliation: Department of Dermatology, Johannes Gutenberg-Universität Mainz, Mainz, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Grabbe
authors.affiliation: BioNTech RNA Pharmaceuticals GmbH, An der Goldgrube 12, 55131 Mainz, Germany.
authors.forename: Heinrich
authors.initials: H
authors.lastname: Haas
authors.affiliation: BioNTech RNA Pharmaceuticals GmbH, An der Goldgrube 12, 55131 Mainz, Germany.|Translational Oncology (TRON), Freiligrathstraße 12, 55131 Mainz, Germany.
authors.forename: Mustafa
authors.initials: M
authors.lastname: Diken
authors.affiliation: Translational Oncology (TRON), Freiligrathstraße 12, 55131 Mainz, Germany.|ResearchCenter for Immunotherapy (FZI), University Medical Center at the Johannes Gutenberg University, Langenbeckstr.1, 55131 Mainz, Germany.
authors.forename: Lena M
authors.initials: LM
authors.lastname: Kranz
authors.affiliation: Instituteof Pharmacy and Biochemistry, Department of Biopharmaceutics and Pharmaceutical Technology, Johannes Gutenberg-Universität Mainz, Mainz, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Langguth
authors.affiliation: BioNTech RNA Pharmaceuticals GmbH, An der Goldgrube 12, 55131 Mainz, Germany.|Translational Oncology (TRON), Freiligrathstraße 12, 55131 Mainz, Germany.|ResearchCenter for Immunotherapy (FZI), University Medical Center at the Johannes Gutenberg University, Langenbeckstr.1, 55131 Mainz, Germany.|Biopharmaceutical New Technologies (BioNTech) Corporation, An der Goldgrube 12, 55131 Mainz, Germany.
authors.forename: Ugur
authors.initials: U
authors.lastname: Sahin
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics / Q000276:immunology; D019496:Cancer Vaccines / Q000276:immunology; D002986:Clinical Trials as Topic; D005079:Excipients; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D008081:Liposomes / Q000737:chemistry*; D008545:Melanoma / Q000276:immunology / Q000628:therapy*; D050997:Nanomedicine; D053758:Nanoparticles / Q000737:chemistry* / Q000627:therapeutic use; D057285:Precision Medicine; D012313:RNA / Q000008:administration & dosage / Q000737:chemistry* / Q000276:immunology; D012333:RNA, Messenger / Q000008:administration & dosage / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D005079:Excipients; D008081:Liposomes; D012333:RNA, Messenger; D012313:RNA
keywords: cancer; drug delivery; lipoplex; liposomes; mRNA; tumor immunotherapy