GD2targeted

GD2-targeted refers to therapies directed against GD2, a disialoganglioside highly expressed on several solid tumors, especially neuroblastoma, some melanoma and sarcomas, with limited normal tissue expression outside the central nervous system and peripheral nerves. GD2 is a glycolipid antigen on the cell surface that has been pursued as an immunotherapy target because cancers often overexpress it while most normal tissues express it only at low levels.

The most established GD2-targeted therapy class is monoclonal antibodies, notably dinutuximab, which binds GD2 to trigger antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity. These antibodies have been approved in certain settings for high-risk neuroblastoma; in Europe dinutuximab beta is approved as well. Treatment regimens often include cytokines to enhance immune activity. Side effects frequently include neuropathic pain, fever, and hypersensitivity reactions due to GD2 presence on peripheral nerves.

Beyond naked antibodies, GD2-targeted strategies include chimeric antigen receptor (CAR) T cells directed at GD2, which are under investigation in pediatric and adult trials; bispecific T-cell engagers or GD2-directed antibody-drug conjugates are also in early-phase development. These approaches aim to improve tumor killing and overcome resistance while maintaining manageable safety profiles.

The term GD2-targeted encompasses ongoing research across neuroblastoma and other GD2-expressing cancers, including melanoma and sarcomas. Regulatory approval varies by region and cancer type, with current clinical use primarily in neuroblastoma settings. Ongoing trials seek to optimize dosing, combinations with checkpoint inhibitors or cytokines, and patient selection based on GD2 expression.