Abstract
Most pathogens establish infection through mucosa, where secretary IgA (sIgA) plays an "immune exclusion" role in humoral defense. Extravasation of intravenously administrated therapeutic IgG mainly relies on convection and/or FcRn-mediated transcytosis from circulation into interstitial space. Active transport of interstitial IgG further across epithelium into mucosa, like sIgA, is a much desired feature for the next generation of therapeutic antibodies, especially for anti-infection purposes. For the first time, we report the engineering of an IgA mimicry of IgG, with its Fc portion in fusion with the 18-aa tail piece (tp) of sIgA and the J chain, possessing sIgA's full binding activity towards Polymeric Immunoglobulin Receptor (pIgR) that mediates mucosa transcytosis. In a Diphtheria toxin receptor (DTR) knockin mouse model, i.v. injected anti-DT IgG(tp)J protected DTR+ cells from deletion upon DT injection. The compact design of IgG(tp)J opens new revenues for more effective therapeutic IgG mimicking some of the important biological functions of IgA.