Product(s) used in this publication: Custom Peptide Synthesis
Intradermal administration of antigen-encoding RNA has entered clinical testing for cancer vaccination. However, insight into the underlying mechanism of RNAuptake, translation and antigen presentation is still limited. Utilizing pharmacologically optimized nakedRNA, the dose-response kinetics revealed a rise in reporter signal with increasing RNA amounts and a prolonged RNA translation of reporter protein up to 30 days after intradermal injection. Dendriticcells (DCs) in the dermis were shown to engulf RNA, and the signal arising from the reporter RNA was significantly diminished after DC depletion. Macropinocytosis was relevant for intradermal RNAuptake and translation in vitro and in vivo. By combining intradermal RNA vaccination and inhibition of macropinocytosis, we show that effective priming of antigen-specific CD8(+) T-cells also relies on this uptake mechanism. This report demonstrates that direct antigen translation by dermal DCs after intradermal nakedRNA vaccination is relevant for efficient priming of antigen-specific T-cells.
Cancer immunotherapy; Dermal dendritic cell; Intradermal vaccination; Macropinocytosis; NakedRNA; RNA vaccine