ArticleMethods in molecular biology (Clifton, N.J.)2026
Generation and Characterization of Bispecific VHH-Derived Surrogate Agonists Mimicking the Function of IL-18.
Article in Methods in molecular biology (Clifton, N.J.), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Interleukin-18 (IL-18) is a promising cytokine for immunotherapy. Besides exploiting the cytokine itself or mutant versions thereof for biomedical applications, bi- and multispecific antibody scaffolds can be harnessed that mimic the function of IL-18 by triggering receptor signaling. In addition to potential advantages with respect of manufacturability, a major benefit in using bispecific antibody derivatives relies in the different structure and sequence of the antibody compared to the cytokine. The activity of IL-18 is normally regulated in a negative feedback loop via IL-18 binding protein (IL-18BP) that binds with high affinities to IL-18 and prevents IL-18 from binding to its receptor. This physiological process is hijacked in certain types of cancer. We have generated VHH-derived bispecific surrogate agonists that are naturally resistant to inhibition by the decoy receptor IL-18BP. In this chapter, we detail protocols about the generation and characterization of IL-18 mimicking bispecifics.
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