A Nature Communications study demonstrated that engineering anti‑CD27 agonists for multivalency and engagement of the inhibitory FcγRIIB receptor substantially enhances antitumor activity. The work shows how antibody architecture and Fc receptor interactions can convert weak agonists into potent immune stimulants in preclinical models. The findings offer a design blueprint for next‑generation costimulatory agonists by linking geometric valency and selective Fc engagement to functional potency. Biotech developers of immuno‑agonists should evaluate Fc engineering and multimerization strategies in lead optimization; regulators will scrutinize safety given the immune‑stimulatory mechanism.