6533b833fe1ef96bd129cade

RESEARCH PRODUCT

FLT3 Ligand as a Molecular Adjuvant for Naked RNA Vaccines

ÖZlem TüreciMustafa DikenUgur SahinJutta PetschenkaSebastian KreiterAbderraouf Selmi

subject

0301 basic medicineChemistrymedicine.medical_treatmentPriming (immunology)chemical and pharmacologic phenomenaImmunotherapyDendritic cellbiochemical phenomena metabolism and nutrition03 medical and health sciences030104 developmental biologyImmune systemAntigenSystemic administrationmedicineCancer researchbacteriaAdjuvantCD8

description

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.

yearjournalcountryeditionlanguage
2016-01-01
https://doi.org/10.1007/978-1-4939-3625-0_11