Assessment of the Effect of Crizanlizumab on Red Blood Cell Adhesion to Endothelial Cells Using a Standardized Endothelium-on-a-Chip Microfluidic Platform

Background: Chronic upregulation of P-selectin (P-sel) on blood cells and the endothelium leads to abnormal red blood cell (RBC) adhesion to endothelial cells, significantly contributing to vaso-occlusive crises (VOCs), which are a major cause of morbidity and mortality in patients with sickle cell disease (SCD). Crizanlizumab (criz, a.k.a. SEG101) is a humanized anti-P-sel monoclonal antibody and has recently been approved by the Food and Drug Administration to reduce the frequency of VOCs in SCD patients. Here, we report in vitro assessment of the effect of criz on patient-specific RBC adhesion to heme-activated human endothelial cells using a standardized endothelialized microfluidic platform, the Endothelium-on-a-chip.