Interleukins & Cytokines
Constructive.bio engineers interleukins and cytokines with site-specific ncAA modifications that achieve receptor-selective signalling, extended half-life through defined PEGylation, and reduced vascular leak syndrome — the dose-limiting toxicity that has historically restricted cytokine therapeutics. Our platform installs modifications at 1–3 precise positions per molecule via fermentation.
The Problem
Cytokines like IL-2, IL-15, and IL-10 show potent anti-tumour activity but signal through multiple receptor complexes, causing severe toxicity. IL-2 binds both the high-affinity IL-2Rαβγ (on regulatory T cells) and intermediate-affinity IL-2Rβγ (on effector T cells and NK cells). Native IL-2 preferentially activates Tregs and causes vascular leak syndrome, limiting its therapeutic utility despite proven efficacy. Random PEGylation to extend half-life further reduces activity unpredictably.
Our Approach
Constructive.bio incorporates ncAAs at positions that selectively modulate receptor binding. For IL-2, ncAA substitutions at the IL-2Rα interface reduce Treg activation while preserving IL-2Rβγ engagement for effector cell stimulation. Site-specific PEGylation via a single azide-bearing ncAA at a defined position provides controlled half-life extension without the heterogeneity of random conjugation. Additional ncAA modifications can attenuate the IL-2Rα interaction to further shift the therapeutic index toward anti-tumour immunity.
Key Capabilities
Receptor-selective cytokine variants through precise ncAA substitution at binding interfaces
Site-specific PEGylation at a single defined position — no random conjugation heterogeneity
Up to 3 simultaneous ncAA modifications per cytokine molecule
Reduced vascular leak syndrome through engineered receptor selectivity