title: FLT3 Ligand as a Molecular Adjuvant for Naked RNA Vaccines.
abstract: Intranodal immunization with antigen-encoding naked mRNA has proven to be an efficacious and safe approach to induce antitumor immunity. Thanks to its unique characteristics, mRNA can act not only as a source for antigen but also as an adjuvant for activation of the immune system. The search for additional adjuvants that can be combined with mRNA to further improve the potency of the immunization revealed Fms-like tyrosine kinase 3 (FLT3) ligand as a potent candidate. Systemic administration of the dendritic cell-activating FLT3 ligand prior to or along with mRNA immunization-enhanced priming and expansion of antigen-specific CD8(+) T cells in lymphoid organs, T-cell homing into melanoma tumors, and therapeutic activity of the intranodally administered mRNA. Both compounds demonstrate a successful combination in terms of boosting the immune response. This chapter describes methods for intranodal immunization with naked mRNA by co-administration of FLT3 ligand, which leads to strong synergistic effects.
authors.affiliation: TRON-Translational Oncology at the University Medical Center of Johannes Gutenberg University, TRON gGmbH, Freiligrathstrasse 12, 55131, Mainz, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Kreiter
authors.affiliation: TRON-Translational Oncology at the University Medical Center of Johannes Gutenberg University, TRON gGmbH, Freiligrathstrasse 12, 55131, Mainz, Germany.
authors.forename: Mustafa
authors.initials: M
authors.lastname: Diken
authors.affiliation: TRON-Translational Oncology at the University Medical Center of Johannes Gutenberg University, TRON gGmbH, Freiligrathstrasse 12, 55131, Mainz, Germany.
authors.forename: Abderraouf
authors.initials: A
authors.lastname: Selmi
authors.affiliation: TRON-Translational Oncology at the University Medical Center of Johannes Gutenberg University, TRON gGmbH, Freiligrathstrasse 12, 55131, Mainz, Germany.
authors.forename: Jutta
authors.initials: J
authors.lastname: Petschenka
authors.affiliation: TRON-Translational Oncology at the University Medical Center of Johannes Gutenberg University, TRON gGmbH, Freiligrathstrasse 12, 55131, Mainz, Germany.
authors.forename: Özlem
authors.initials: Ö
authors.lastname: Türeci
authors.affiliation: TRON-Translational Oncology at the University Medical Center of Johannes Gutenberg University, TRON gGmbH, Freiligrathstrasse 12, 55131, Mainz, Germany. ugur.sahin@tron-mainz.de.
authors.forename: Ugur
authors.initials: U
authors.lastname: Sahin
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology* / Q000276:immunology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology; D008565:Membrane Proteins / Q000008:administration & dosage* / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000008:administration & dosage* / Q000276:immunology; D014611:Vaccination / Q000379:methods
chemical_list: D000276:Adjuvants, Immunologic; D008565:Membrane Proteins; D012333:RNA, Messenger; C084881:flt3 ligand protein
keywords: Cancer vaccination; Dendritic cell; FLT3 ligand; IVT-RNA; Immunotherapy; Intranodal injection; RNA vaccine; Vaccine adjuvants