Fenretinide (4-HPR) as immunostimulator of the antibody-dependent (ADCC) and antibody-independent NK cell mediated cytotoxicity (AICC) on neuroblastoma

Introduction: A current approach to consolidate remissions in the treatment of neuroblastoma (NB) consists of an anti-GD2-directed immunotherapy plus cytokines in combination with 13-cis retinoic acid. Fenretinide (4-HPR) is a synthetic derivative of retinoic acid and it is in clinical development for the treatment of high-risk NB patients. Since 4-HPR induces apoptosis mainly via the accumulation of ceramides, which are degraded to GD2, we evaluated its effect on anti-GD2-directed immunotherapies. Methods/Results: We demonstrate that increased GD2 expression by 4-HPR results in improved ch14.18 mediated ADCC by…