Alpha-1,3-galactosyl epitope (Alpha-gal) (Alpha-gal)

The alpha-1,3-galactosyl epitope (alpha-gal) is a carbohydrate antigen expressed on the cell surfaces of most mammals but is absent in humans due to the evolutionary loss of the alpha-1,3-galactosyltransferase enzyme (Galili, 2013). Humans naturally produce high levels of anti-alpha-gal antibodies, which are responsible for the hyperacute rejection of xenografts. The HyperAcute-Renal (Sograzepumatucel-L) platform exploits this natural immunity by engineering renal cancer cells to express alpha-gal epitopes on their surface (Link et al., 2010). Upon administration, these engineered cells are recognized by the patient's pre-existing anti-alpha-gal antibodies, which then recruit Fcγ receptor-bearing effector cells, such as natural killer cells and macrophages. This recruitment triggers antibody-dependent cellular cytotoxicity (ADCC) and complement-mediated lysis of the vaccine cells, leading to the release of tumor-associated antigens. These antigens are subsequently captured by dendritic cells to prime a systemic, polyvalent T-cell response against the patient's endogenous tumor (Whalen et al., 2014).

Other names

Galα1-3Galβ1-4GlcNAcα-galGal-alpha-1,3-GalXenotransplantation antigenGal epitope

Induction of antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) via recruitment of Fcγ receptor-bearing effector cells to alpha-gal-expressing tumor cells, leading to the release of tumor antigens and systemic T-cell activation.