Agonistic antibodies present a compelling approach to treating human diseases, but their discovery has been severely limited by the difficulty of identifying them effectively. Using a mix of experimental and computational approaches, we generated bispecific agonist antibodies that activate the IL-18 pathway. These antibodies activate the IL-18 receptor directly, inducing IFNγ while sparing myeloid cells, a tolerability issue associated with IL-18 and its muteins, thus offering an activity driven towards anti-tumor effects.

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