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

• DOI: 10.1016/j.nano.2017.10.015
• Publication Date: 2017-11-08T20:30:48Z
• Authors: Damien Carignan; Sabine Herblot; Marie-Ève Laliber...; Marilène Bolduc; Michel Duval; Pierre Savard; Denis Leclerc
• Keywords: Interferon-alpha; Dendritic Cells; Immunity, Innate; 3. Good health; Killer Cells, Natural; Potexvirus; 03 medical and health sciences; 0302 clinical medicine; Toll-Like Receptor 7; Toll-Like Receptor 8; Leukocytes, Mononuclear; Cytokines; Humans; Nanoparticles; Chemokines; Cells, Cultured

Rod-shaped virus-like nanoparticles (VLNP) made of papaya mosaic virus (PapMV) coat proteins (CP) self-assembled around a single stranded RNA (ssRNA) were showed to be a TLR7 agonist. Their utilization as an immune modulator in cancer immunotherapy was shown to be promising. To establish a clinical relevance in human for PapMV VLNP, we showed that stimulation of human peripheral blood mononuclear cells (PBMC) with VLNP induces the secretion of interferon alpha (IFNα) and other pro-inflammatory cytokines and chemokines. Plasmacytoid dendritic cells (pDCs) were activated and secreted IFN-α upon VLNP exposure. Monocyte-derived dendritic cells upregulate maturation markers and produce IL-6 in response to PapMV VLNP stimulation, which suggests the activation of TLR8. Finally, when co-cultured with NK cells, PapMV induced pDCs promoted the NK cytolytic activity against cancer cells. These data obtained with primary human immune cells further strengthen the clinical relevance of PapMV VLNPs as a cancer immunotherapy agent.