Fact Sheet: Conditional Cytokine Activation - Dual-specificity Fab engineering

IL-12 is among the most potent anti-tumour cytokines, but systemic toxicity has limited its clinical development for close to thirty years.

This fact sheet sets out how FairJourney Bio engineered a dual-binding Fab that keeps IL-12 masked until it reaches the tumour.

The molecule binds two unrelated antigens competitively, at affinities separated by design, matching two clinical benchmark antibodies simultaneously, one of them deliberately at low affinity. Unmasking of IL-12 was shown to be FN-EDB-dependent in both biochemical and cell-based assays, with the predicted therapeutic window derived from QSP modelling rather than in vivo measurement.

The switch-arm format is not specific to IL-12. Given a suitable tissue-restricted antigen, the same architecture can in principle gate other cargoes.

Download the fact sheet for the engineering approach, the affinity data, and what this means for programmes working with complex formats.