TriMix – a rationally designed novel adjuvant
- NDendritic cell (DC) specific enhancer of T cell response
- NBenefit demonstrated in various preclinical models
- NClinically validated in 4 ex-vivo DC studies & clinical safety shown for IN
TriMix has unique adjuvant capacity delivering a triple action:
The three mRNA constructs of TriMix code for potent Dendritic Cell (DC) activation molecules: a human Cluster of Differentiation 40 Ligand (CD40L), a Constitutively Active Toll-like Receptor 4 (caTLR4) and human CD70, thereby acting on 3 different immuno-stimulatory pathways.
HuCD40L mimics the interaction between DCs and CD4+ T-cells, activating the DCs to present the antigens. It also leads skewing towards activated T helper 1 CD4+ T cells (Th1) that, through secretion of IL-2, activate cytolytic CD8+ T-cells. CD40L–CD40 interactions mediate one of the most potent DC activating signals
caTLR4 mimics the danger signals combated by the immune system upon bacterial infection due to lipopolysaccharide. As such, caTLR4 is a strong activator of the innate immune system and thus of DCs.
CD70 is a member of the tumour necrosis factor (TNF) superfamily of co-stimulatory molecules and is the ligand of CD27, which is constitutively expressed on B cells, naïve T cells, and on several subsets of memory T-cells. Upon T-cell activation, CD27 expression is regulated during several rounds of division and differentiation towards effector T-cells. CD27 ligation promoting the proliferation of primed T-cells is a key contributor to the formation of effector and memory T-cell populations. CD70 is crucial for priming CD8+ T-cell responses.
Inherent immunostimulatory effect
mRNA also has an inherent immunostimulatory effect that strongly activates the innate immune system, this further improves the effectiveness of RNA-based immunotherapies. Nevertheless, TriMix exerts its strongest effect by in vivo expression in APCs, especially dendritic cells (DCs), of the 3 proteins encoded by its mRNAs. TriMix already showed safety and strong efficacy in humans.