Therapeutically targeting glypican-2 via single-domain antibody-based chimeric antigen receptors and immunotoxins in neuroblastoma

Neuroblastoma is a childhood cancer that remains an important clinical challenge. It is fatal in almost half of the patients despite advances in multimodal treatments. In this report, we show that the cell surface glycoprotein glypican-2 (GPC2) is overexpressed in neuroblastomas when compared with normal tissues and that a high expression level is correlated with poor survival of neuroblastoma. We also describe that GPC2 has proliferative effects in neuroblastoma via activating Wnt signaling and its downstream target genes including N-Myc, a major driver for neuroblastoma tumorigenesis. We have produced the immunotoxins and chimeric antigen receptor T cells that target GPC2 and exhibit promising antitumor activities in cell and mouse models. This study suggests GPC2 as a promising target in neuroblastoma.