IGFBP7-targeting monoclonal antibodies attenuate the endothelial inflammatory niche in psoriasis-like inflammation

Psoriasis is sustained by immune–endothelial interactions that support leukocyte recruitment into inflamed skin. We previously showed that endothelial IGFBP7 disrupts the glycocalyx and promotes T-cell extravasation. Here, we developed and compared monoclonal antibodies against human IGFBP7. Reanalysis of longitudinal single-cell RNA sequencing from risankizumab-treated psoriasis skin identified an IGFBP7-positive vascular endothelial state that was enriched in baseline lesions and reduced during treatment. Cutaneous IGFBP7 expression also correlated with Psoriasis Area and Severity Index in an independent cohort. Three mouse monoclonal antibodies were generated against recombinant human IGFBP7, and all three recognized recombinant murine IGFBP7. CMC0667 showed the strongest reference-antibody cross-competition (IC₅₀, 5.72 nM), while surface plasmon resonance confirmed direct nanomolar-range binding to IGFBP7 (k a , 2.86 × 105 M−1 s−1; k d , 1.35 × 10−2 s−1; kinetic K D , 47.4 nM). In cytokine-stimulated HMEC-1 cells, the antibodies increased hyaluronic acid and heparan sulfate signals, reduced endothelial activation, improved junction-associated gene expression, and decreased FITC-dextran permeability and CD3⁺CD4⁺ T-cell transendothelial migration. In imiquimod-treated mice, all three antibodies reduced epidermal hyperplasia, keratinocyte proliferation, inflammatory and chemotactic gene expression, and cutaneous T-cell accumulation. CMC0667 showed the most consistent overall activity. Together, these data identify CMC0667 as the lead anti-IGFBP7 antibody for further preclinical optimization.