Inspired by the studies on the relationship between the agonistic activities of TNFRSF antibodies and FcγRIIB dependency, we have proposed a cross-link antibody (xLinkAb) working model to optimize therapeutic antibodies by engineering Fc with selective FcγRIIB binding ability to match a desirable Fab to achieve tumor-targeted agonistic activity (Figure 4). Here, FCGR2B is linked to neoplasm.