O-acetylated GD2 ganglioside (OAcGD2) (OAcGD2)

O-acetylated GD2 (OAcGD2) is a tumor-associated ganglioside characterized by the addition of an acetyl group to the C9 position of the terminal sialic acid residue of the GD2 ganglioside (Cerato et al., 2022). It is highly expressed on the surface of various neuroectoderm-derived malignancies, including neuroblastoma, melanoma, and small cell lung cancer, while remaining virtually absent from normal tissues (Alvarez-Rueda et al., 2011). A critical distinction between OAcGD2 and its precursor GD2 is that OAcGD2 is not expressed on peripheral nerve fibers, which are responsible for the severe neuropathic pain associated with anti-GD2 therapies like dinutuximab (Terme et al., 2013). This unique expression profile makes OAcGD2 an ideal target for immunotherapy, as it allows for the selective destruction of tumor cells while potentially sparing patients from dose-limiting neurotoxicity. Therapeutic agents currently under investigation include the monoclonal antibody 8B6 and its humanized derivatives, which induce tumor cell death through antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) (Cochrane et al., 2016). Additionally, OAcGD2-targeted chimeric antigen receptor (CAR) T-cell therapies are being developed to provide more potent and durable anti-tumor responses in patients with GD2-positive cancers (Fleurence et al., 2016).

Other names

O-acetyl-GD29-O-acetyl-GD2OAcGD2 gangliosideO-acetylated disialoganglioside GD2

Antibody-dependent cellular cytotoxicity (ADCC), Complement-dependent cytotoxicity (CDC), and induction of apoptosis.