A chimeric antigen receptor (CAR) designed to target pediatric and adult malignancies expressing GD2 such as neuroblastoma, glioblastoma, 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 IgM antibody. This anti-GD2 CAR represents a powerful new tool to redirect T cells against GD2.
A previous publication (Prapa M et al. Oncotarget 2015) shows 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.
Further investigations have been conducted against human glioblastoma multiforme providing relevant efficiency in cell lines and primary tumor samples as well as safety during extensive in vitro and in vivo investigations. Extensive anti-cancer cytokine investigations were performed to precisely dissect the mechanisms of action. No signs of toxicity have been observed in animal models even in an orthotopic model and after systemic intravenous infusions.
These results prompted further investigations into treatments for malignant melanoma, Ewing Sarcoma, small cell lung cancer and other GD2-positive malignancies. More information, including the unpublished manuscript and data, is available under a confidentiality agreement.
CAR, T Cell Therapy, Anti-GD2-BB-zeta chimeric receptor, cancer, cell therapy, gene therapy, immunotargeting, neuroblastoma, GD2 expressing tumors, TRAIL, glioblastoma, retinoblastoma, Ewing sarcoma, tumors, rhabdomyosarcoma, osteosarcoma, leiomyosarcoma, liposarcoma, fibrosarcoma, small cell lung cancer, melanoma
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. (Article available on request or here)
A recent review on GD2 targeting is located here: http://www.ncbi.nlm.nih.gov/pubmed/25604432
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