Disialoganglioside GD2 and B7 homolog 3 (CD276) (GD2/B7-H3)

Disialoganglioside GD2 and B7 homolog 3 (CD276) are two prominent tumor-associated antigens frequently co-expressed on the surface of various pediatric and adult solid tumors, including neuroblastoma, osteosarcoma, and diffuse intrinsic pontine glioma (DIPG) (Mount et al., 2018; Majzner et al., 2019). GD2 is a disialoganglioside involved in cell adhesion and signal transduction, while B7-H3 is an immune checkpoint member of the B7 family that contributes to tumor immune evasion and progression (UniProt, 2023; Seaman et al., 2017). Targeting these molecules simultaneously is a therapeutic strategy designed to enhance tumor specificity and mitigate the risk of antigen escape, which is a common cause of relapse in single-target therapies (Moussa et al., 2021). Bispecific chimeric antigen receptor (CAR) T-cells and bispecific antibodies are being developed to recognize cells expressing both markers, potentially improving the therapeutic index (ClinicalTrials.gov, 2023). By requiring the presence of both antigens for full activation, these therapies aim to reduce "on-target, off-tumor" toxicities, such as the intense pain and neurotoxicity associated with GD2 expression on normal peripheral nerve fibers (Sait & Modak, 2017). This combinatorial approach represents a significant advancement in the precision of immunotherapy for refractory solid malignancies.

Other names

GD2 and CD276Ganglioside GD2 and B7-H3GD2/B7-H3 dual targetGD2 and B7-H3 co-expression

Dual-antigen recognition and T-cell mediated cytotoxicity, Logic-gated (AND-gate) CAR-T cell activation, Bispecific antibody-mediated T-cell engagement