GD2-targeted immunotherapy of neuroblastoma

Disialoganglioside GD2 is highly expressed on neuroectodermal tumors and sarcomas, but only weakly expressed on limited normal tissues. It has been identified as a marker for a subset of breast cancer cells and mesenchymal stromal cells with stemness potentials and shown to be involved in cancer cell adhesion, invasion and viability, and immune cell activation. Active and passive immunotherapeutic strategies, including vaccines, peptide mimotopes, monoclonal antibodies, bispecific antibodies, anti-idiotype antibody, immunocytokine, and chimeric antigen receptor T-cell, have been investigated for the treatment of GD2-expressing cancers. A randomized trial of isotretinoin ± Dinutuximab, a chimeric anti-GD2 monoclonal antibody, in high-risk neuroblastoma showed a significant improvement in 2-year event-free survival and overall survival in the immunotherapy group. Dinutuximab has since been approved for the treatment of neuroblastoma, marking the first new agent targeting a glycolipid molecule. Its success demonstrates that cancer-associated carbohydrate antigens could be an effective target for cancer immunotherapy.