Immunotherapeutic Strategies Targeting GD2-Expressing Malignancies.

GD2, a tumor-associated carbohydrate antigen, has been validated as a promising immunotherapeutic target for the treatment of high-risk neuroblastoma. Historically, cancer therapies have largely focused on protein targets. However, the FDA approval of dinutuximab, a GD2-specific monoclonal antibody, in 2015 marked a significant shift by establishing carbohydrates as viable therapeutic targets. Since then, anti-GD2 has become a key component of the standard treatment regimen for high-risk neuroblastoma. Beyond neuroblastoma, GD2 is also expressed in several other malignancies, including melanoma, glioma, small cell lung cancer, and sarcoma. A wide array of therapeutic strategies targeting GD2 has been developed, encompassing murine, chimeric, and humanized antibodies; bispecific antibodies; immunocytokines; chimeric antigen receptor (CAR)-T and CAR natural killer T (NKT) cells; and vaccine-based approaches. A thorough understanding of the strengths and limitations of each of these modalities is essential to inform the design of more effective combination therapies and to improve outcomes for patients with GD2-expressing tumors.