FIGURE 4.

xLinkAb working model: the role of FcγRIIB in the oligomerization of TNFSFR-IgG-FcγRIIB complexes. xLinkAb TNFRSF agonistic antibody Fab arms binding to TNFRSF is insufficient to cluster and activate TNFRSF target; xLinkAb IgG-TNFRSF complex engages FcγRIIB with its engineered Fc selectively for FcγRIIB binding, leading to the formation of oligomic TNFRSF-IgG- FcγRIIB complexes and clustering of TNFRSF and signaling activation. The initial step should be IgG-Fab binding to TNFRSF, which is followed by TNFRSF-IgG-Fc binding to FcγRIIB forming TNFRSF-IgG-FcγRIIB complex and secondary clustering of TNFRSF. Activation of TNFRSF signaling depends on the formation of the multivalent TNFRSFs-IgGs-FcγRIIBs complexes and TNFRSF super-clustering.