Anti-Glypican 2 Chimeric Antigen Receptor (CAR) Containing CD28 Hinge And Transmembrane Domains For Treating Neuroblastoma
Neuroblastomas are the most common extracranial solid tumors in pediatric patients, with 700-800 new cases annually in the United States. Metastatic neuroblastomas have a five-year survival rate of 50% and account for 15% of all pediatric cancer deaths. As such, more effective treatments against high-risk neuroblastomas are urgently needed. Glypican-2 (GPC2) is a cell surface protein that is highly expressed in neuroblastomas and other cancers, including medulloblastoma, retinoblastoma, small-cell lung cancers, uterine carcinosarcomas and high-grade gliomas, which makes GPC2 an attractive candidate for targeted therapy in solid tumors.
Researchers at the National Cancer Institute’s (NCI) Center for Cancer Research have developed a novel Chimeric Antigen Receptor (CAR) specific for GPC2 that includes a potent anti-GPC2 antibody CT3 and a CD28 hinge and transmembrane domains. CT3 has been shown to specifically target GPC2-expressing neuroblastoma, medulloblastoma, and retinoblastoma cell lines. CT3.28H.BBζ CAR T cells were shown to be more potent against neuroblastoma cells than the previous anti-GPC2 CAR T cells in vitro and in vivo. These preclinical data suggest that CT3.28H.BBζ CAR T cells may be further developed as therapeutics for patients with neuroblastoma and other GPC2-positive cancers. Incorporation of the CD28 hinge and transmembrane domains increases the potency of the CT3 CARs against neuroblastoma cells.
- Immunotherapeutic treatments of GPC2-positive pediatric malignancies, including neuroblastoma, medulloblastoma, retinoblastoma, and a subset of acute lymphocytic leukemias
- Immunotherapeutic treatments of GPC2-positive adult cancers, including small-cell lung cancers, uterine carcinosarcomas and high-grade gliomas
- CT3.28H.BBζ CAR available for immediate testing
- CT3 antibody with high GPC2 binding specificity leading to successful targeting
- CT3 antibody with high GPC2 binding specificity leading to lower potential side-effects
- Increased potency against neuroblastoma
- Potential immunotherapy for several GPC2-positive cancer types with few treatment options