Activation of innate immunity in primary human cells using a plant virus derived nanoparticle TLR7/8 agonist

Mechanism of action of PapMV nanoparticles in immune cells. Immune cells [like plasmacytoid dendritic cells (pDCS), myeloid dendritic cells (mDCs), macrophages and monocytes] internalize PapMV nanoparticles that accumulate into the endosome. The drop of the pH in the endosome induces a conformation change into the PapMV coat protein (CP) that leads to the disassembly of the nanoparticle leading to the release the ssRNA. The ssRNA gets rapidly degraded and produces the small oligos that engage and activate the TLR7 and/or 8. This activation is followed by a cascade of signalization events that induces innate immunity. Transcription of genes leading to production of the pro-inflammatory cytokines and chemokines, including IFN-α is crucial in the anti-cancer immune response triggered by PapMV nanoparticles. The activation of immune cells also leads to the activation of NK cells and the development of an anti-cancer immune response able to lyse acute lymphoblastic lymphoma (ALL) cancer cells.114