Fig. 1

Schematic representation of trafficking mechanism for a conventional and recycling antibody. a Antibody–antigen complexes taken up by cells through non-specific pinocytosis or endocytosis are shuttled to sorting endosomes. In sorting endosome, the complex binds FcRn at acidic pH 6.0. A conventional antibody bound to an antigen at pH 6.0, is preferentially directed toward recycling pathways mediated by FcRn rather than transitioning from sorting endosome to the lysosome for lysosomal degradation. For an engineered recycling/sweeping antibody, reduced antigen affinity at pH 6.0 leads to dissociation of the antigen from the antibody–antigen complex. The dissociated antigen is trafficked towards the lysosome for degradation. Sweeping antibodies having a higher affinity to FcRn at pH 7.4 undergo FcRn mediated endocytosis. This higher affinity to FcRn leads to higher persistence of the antibody, and reduced availability of antigen