Figure 2.

Schematic of the molecular Trojan horse (MTH) technology to ferry biologic TNF-α inhibitors (TNFIs) into the brain. The TNFI of interest in the figure is a tumor necrosis factor α receptor (TNFR). A fusion protein of TNFR and a blood-brain barrier (BBB) MTH, such as the chimeric monoclonal antibody against the mouse transferrin receptor (cTfRMAb), can be engineered and this is designated as cTfRMAb-TNFR. Following systemic injection, the cTfRMAb-TNFR fusion protein binds to the BBB transferrin receptor (TfR)1 and is transported across the BBB from blood to brain via the BBB TfR that undergoes receptor-mediated transcytosis.² Once in the brain, the TNFR domain of the fusion protein can sequester excess TNF-α in the brain.³