UC-1V150, a potent TLR7 agonist capable of activating macrophages and potentiating mAb-mediated target cell deletion

Abstract

Toll-like receptors (TLR) are critical mediators of the immune system with their activation linked to infection, inflammation and the pathogenesis of immune diseases including autoimmunity and cancer. For this reason, over the last 2 decades, TLR and their associated signalling pathways have been targeted therapeutically to enhance innate and adaptive immunity. Several TLR ligands, both endogenous and synthetic are at various phases of clinical testing, and new ligands are continually emerging. Agonists of TLR7 are known immune response modifiers, simultaneously stimulating several cell types, resulting in immune cell activation and cytokine and chemokine release. The immune stimulating properties of the TLR7 agonist Imiquimod has also been exploited for use in the treatment of malignant superficial tumours of the skin. Here, we investigated a novel TLR7 agonist UC-1V150 and demonstrate it activates both human and mouse myeloid cells in vitro and in vivo, to deliver potent FcγR-mediated engulfment of opsonized target cells.

Keywords: Fc gamma receptor; macrophage; target cell deletion; toll-like receptors.