December 2022 — Vol 142 No 12

DSG targeting‒dependent localized skin protection by the BsAb.

Hsue et al. used a mouse model of vitiligo to test whether a biphasic antibody, binding to both desmoglein and IFN-γ, could prevent skin depigmentation. After the transfer of Thy1.1+ transgenic PMEL CD8+ T cells and bone marrow derived dendritic cells loaded with the PMELcognate peptide into irradiated Krt14-Kitl* mice, they developed rapid epidermal depigmentation. Administration of an anti-desmoglein antibody (top panel) into the right footpad had no effect on depigmentation. Administration of an anti-IFN-γ antibody (middle panel) prevented depigmentation on both footpads, indicating a systemic effect of the locally administered antibody. By contrast, administration of the biphasic DSG/IFN-γ antibody prevented depigmentation only at the injected footpad (bottom panel). These data demonstrate that desmoglein-tethering of bioactive molecules like antiIFN-g can promote long lasting region-specific efficacy in the skin. For details see page 3294.