Immunocytokines
Constructive.bio constructs immunocytokines with defined antibody-to-cytokine ratios through site-specific ncAA-mediated click chemistry conjugation. Unlike genetic fusions — which produce fixed 1:1 or 2:1 formats with compromised folding and reduced activity — our approach enables tuneable stoichiometry (1:1, 1:2, or 2:1), maintained cytokine bioactivity, and homogeneous products manufactured with batch consistency.
The Problem
Immunocytokines — antibodies fused to cytokines for tumour-targeted immune activation — suffer from fundamental format limitations. Genetic fusions constrain the cytokine to the N- or C-terminus, often impairing folding, reducing cytokine activity by 10–100×, and creating aggregation-prone molecules. The fixed stoichiometry of genetic fusions (typically 2 cytokines per antibody) limits dose optimisation. Manufacturing these bifunctional proteins at scale with consistent quality remains challenging.
Our Approach
Constructive.bio incorporates ncAAs with bio-orthogonal handles into both the antibody and cytokine components independently. The antibody bearing azide ncAAs at defined Fc positions is conjugated to the cytokine bearing complementary DBCO or TCO groups via click chemistry. This modular approach allows: selection of optimal conjugation sites on both components independently, tuneable stoichiometry by varying the number of ncAA positions, and maintained native folding of both antibody and cytokine since neither sequence is disrupted by a genetic fusion.
Key Capabilities
Tuneable antibody-to-cytokine stoichiometry: 1:1, 1:2, or 2:1 ratios
Click chemistry conjugation preserves native folding and cytokine bioactivity
Modular assembly — optimise antibody and cytokine components independently
Homogeneous product with defined composition — no heterogeneous fusion mixtures