A chimeric antigen receptor (CAR) designed to target pediatric and adult malignancies expressing GD2 such as neuroblastoma, glioma, retinoblastoma, Ewing's family of tumors, rhabdomyosarcoma, osteosarcoma, leiomyosarcoma, liposarcoma, fibrosarcoma, small cell lung cancer and melanoma has been developed. This CAR was made by replacing the anti-CD19 targeting moiety of the anti-CD19-BB-zeta CAR previously created at St. Jude with the ScFv portion of a novel anti-GD2 antibody.
A July 20, 2015 Oncotarget publication shows these transduced T cells expressed high levels of anti-GD2 CAR and exerted a robust and specific anti-tumor activity in 4-and 48-hour cultures with neuroblastoma cells. These results were confirmed in a xenograft model, where anti-GD2 CAR T cells infiltrating tumors and persisting into blood circulation induced massive apoptosis of neuroblastoma cells and completely abrogated tumor growth. This anti-GD2 CAR represents a powerful new tool to redirect T cells against GD2. The preclinical results of this study warrant clinical testing of this approach in neuroblastoma and other GD2-positive malignancies.
CAR, T Cell Therapy, Anti-GD2-BB-zeta chimeric receptor, cancer, cell therapy, gene therapy, immunotargeting, neuroblastoma, GD2 expressing tumors, TRAIL
Granted Patents or Published Applications
International PCT patent application published May 2, 2013 as WO 2013/061273; pending applications in the U.S., Europe.
Related Scientific References
Prapa, M., Caldrer, S., Spano, C., Bestagno, M., Golinelli, G., Grisendi, G., Petrachi, T., Conte, P., Horwitz, E., Campana, D., Paolucci, P., & Dominici, M. (2015). A novel anti-GD2/4-1BB chimeric antigen receptor triggers neuroblastoma cell killing. Oncotarget, 5. http://www.ncbi.nlm.nih.gov/pubmed/26298772
A recent review on GD2 targeting is located here: http://www.ncbi.nlm.nih.gov/pubmed/25604432
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