A Phase 1/2 Study of Lentiviral-Mediated Ex-Vivo Gene Therapy for Pediatric Patients with Severe Leukocyte Adhesion Deficiency-I (LAD-I): Results from Phase 1

Introduction: LAD-I is a rare inherited disorder of leukocyte (primarily neutrophil) adhesion to endothelial cell surfaces, migration, and chemotaxis resulting from ITGB2 gene mutations encoding for the β2-integrin component, CD18. Severe LAD-I (i.e., CD18 expression on <2% of PMNs) is characterized by recurrent severe infections, impaired wound healing, and childhood mortality. Although allogeneic hematopoietic stem cell transplant (alloHSCT) is potentially curative, its utilization and efficacy are limited by HLA-matched donor availability and risk of graft-versus-host disease (GVHD). RP-L201-0318 (clinical trials.gov # NCT03812263) is a phase 1/2 open-label clinical trial evaluating the safety and efficacy of autologous CD34+ cells transduced with a lentiviral vector (LV) carrying the ITGB2 gene encoding for CD18 (Chim-CD18-WPRE) in severe LAD-I.