Assessing the therapeutic potential of a panel of novel VCAM-1 antibodies using microfluidic and three-dimensional in vitro models of vascular inflammation Article Swipe
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· 2025
· Open Access
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· DOI: https://doi.org/10.1093/abt/tbaf025
· OA: W4415948526
Objective Antibodies against vascular cell adhesion molecule (VCAM)-1 represent an attractive strategy for atherosclerosis and cardiovascular disease management due to their ability to selectively block leukocyte-endothelial interactions involved in inflammatory cell recruitment. Herein, seven novel anti-VCAM-1 monoclonal antibodies (mAbs) generated from phage display biopanning were tested using a series of in vitro models of cell recruitment to determine their potential utility for treating atherosclerosis. Methods and Results We assessed the inhibitory effects of the test antibodies on cell adhesion and transmigration using a series of in vitro assays that incorporated three-dimensional microfluidics and collagen hydrogel models. In summary, each of our mAb candidates were found to reduce RAW264.7 monocyte adhesion to activated SVEC4–10 endothelial monolayers under static conditions. Subsequently, the three most effective candidates from this assay—2E2, 3C12, and 3H4—were shown to inhibit monocyte adhesion to endothelial microvessels under flow conditions and monocyte transmigration into endothelialized gel matrices under static conditions. Conclusion These results indicate that our novel anti-VCAM-1 mAbs can effectively inhibit monocyte adhesion and transmigration in vitro, supporting the therapeutic rationale of VCAM-1 immunoblockade for the targeted treatment of atherosclerosis.
