Circulating free and low-density lipoprotein-bound GD2 can compete

Introduction: GD2 is a ganglioside expressed on neuroblastoma cell membranes and shed into the circulation, where it primarily circulates bound to low-density lipoprotein (LDL). We questioned whether LDL-bound GD2 could interfere with the binding of therapeutic anti-GD2 monoclonal antibodies (like dinutuximab) to neuroblastoma cells. Methods: The GD2-expressing neuroblastoma cell line IMR5 was stained with an anti-GD2 antibody tagged with allophycocyanin (APC) at the lowest possible saturating concentration, and mean fluorescence intensity was measured by flow cytometry after Results: Free and LDL-bound GD2 reduced anti-GD2-APC antibodies' binding to IMR5 cells Conclusions: At concentrations found in patients with high-risk neuroblastoma, both free GD2 and LDL-bound GD2 blocked anti-GD2 antibody binding to neuroblastoma cells. These data suggest that circulating GD2-LDL could impact the efficacy of therapeutic anti-GD2 antibodies administered to patients with a high disease burden during induction therapy or at relapse and may have therapeutic implications for GD2-directed adoptive cellular therapies.