Motolimod

Motolimod is an agonist of toll-like receptor 8 (TLR8).¹ It increases the production of TNF-α and IL-12 in human peripheral blood mononuclear cells (PBMCs; EC₅₀s = 140 and 120 nM, respectively), monocytes, and myeloid dendritic cells. Motolimod also increases IFN-γ production in natural killer (NK) cells and increases cytolysis in K562 NK cell-sensitive leukemia cells when used at concentrations of 167 and 500 nM for 48 hours. It increases plasma levels of a group of human cytokines, including IL-6, IL-12p70, TNF-α, MCP-1, and MIP-1β, in NOD-scid IL2ry^null (NSG) mice reconstituted with human immune system (NSG-HIS) when administered at doses of 1.5 and 15 mg/m².² Motolimod, when used in combination with pegylated liposomal doxorubicin (PLD), reduces tumor growth and increases tumor infiltration of monocytes and T cells in an ovarian cancer NSG-HIS mouse model.

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1. Lu, H., Dietsch, G.N., Matthews, M.A., et al. VTX-2337 is a novel TLR8 agonist that activates NK cells and augments ADCC. Clin Cancer Res. 18(2), 499-509 (2012).

2. Monk, B.J., Facciabene, A., Brady, W.E., et al. Integrative development of a TLR8 agonist for ovarian cancer chemoimmunotherapy. Clin Cancer Res. 23(8), 1955-1966 (2017).