Neuroblastoma cells highly express the disialoganglioside GD2, a
tumor-associated
carbohydrate antigen, which is also expressed in neurons, skin melanocytes, and peripheral nerve fibers.
Immunotherapy with monoclonal anti-GD2
antibodies has a proven efficacy in clinical trials and is included in the standard treatment for children with high-risk
neuroblastoma. However, the strong neuro-toxicity associated with anti-GD2
antibodies administration has hindered, until now, the possibility for dose-escalation and protracted use, thus restraining their therapeutic potential. Strategies to increase the efficacy of anti-GD2
antibodies are actively sought, with the aim to enable chronic treatments that could eradicate
minimal residual disease and subsequent relapses, often occurring
after treatment. Here, we report that Nanofenretinide and Nanospermidine improved the expression of GD2 in
neuroblastoma cells (CHP-134) and provided different effects in combination with the anti-GD2 antibody
naxitamab. In particular, Nanofenretinide significantly increased the cytotoxic effect of
naxitamab while Nanospermidine inhibited cell motility at extents proportional to
naxitamab concentration. In
neuroblastoma cells characterized by a low and heterogeneous basal expression of GD2, such as SH-SY5Y, which may represent the cell heterogeneity in
tumors after
chemotherapy, both Nanofenretinide and Nanospermidine increased GD2 expression in approximately 50% of cells, thus shifting the
tumor population towards improved sensitivity to anti-GD2
antibodies.