The healthy immune system extinguishes infections while preserving the body’s integrity and preventing inflammatory reactions against harmless components through mechanisms of immune tolerance.
Autoimmune diseases and allergies are conditions where immune tolerance fails.
Most current treatments suppress immune cells irrespective of the components they recognize (their specific antigens), thereby compromising the defense against infection and immune surveillance. A key advantage of antigen-specific immune tolerance induction (such as the Topas approach) is the potential to specifically target pathogenic immune reactions while sparing desired immunity.
Liver sinusoidal endothelial cells (LSECs) are constantly exposed to bloodborne antigens (mostly gut-derived) that they take up and present effectively to naïve T-cells, a central type of immune cell.
Given the need to induce and preserve tolerance to innocuous non-replicating antigens, LSECs are poised to promote immune tolerance. Through their ability to activate a key anti-inflammatory mediator (latent TGF-β) on their surface, LSECs support the induction of anti-inflammatory regulatory T-cells (Tregs), a critically important type of immune cell for maintaining immune tolerance.
At Topas we mimic such bloodborne antigens by our nanoparticle conjugates (NPCs), which target LSECs and in turn lead to antigen-specific Treg generation. The Topas nanoparticles are small polymer-coated superparamagnetic iron oxide particles (SPIONS) conjugated with disease-relevant peptides. They are efficiently taken up into endosomal compartments of LSECs.