Neuroblastoma is a rare pediatric cancer with approximately 1,000 new cases arising annually. Current therapies have a less than forty-five percent (45%), three-year survival rate which demonstrate a need for a more effective treatment against this disease. Glypican-2 (GPC2) is a cell surface protein that is preferentially expressed in pediatric cancers including neuroblastoma, which makes GPC2 an attractive candidate for targeted therapy. Researchers at the National Cancer Institute’s (NCI) Laboratory of Molecular Biology have developed and isolated two new antibodies that target GPC2 (CT3 and CT5). These new antibodies have been shown to specifically target GPC2-expressing neuroblastoma, medulloblastoma, and retinoblastoma cell lines. These GPC2 antibodies can be used as either independent agents or targeting domains in recombinant immunotoxins (RITs), antibody-drug conjugates (ADCs), and chimeric antigen receptors (CARs). Significantly, RITs and CARs (using the CT3 clone) have shown specific killing activity against GPC2-positive neuroblastoma cells, strongly supporting that these candidates may be further developed as therapeutics for patients with GPC2-positive pediatric cancers.