Natural human anti-alpha-Gal antibody (Anti-Gal)

Natural human anti-alpha-Gal antibodies are the most abundant naturally occurring antibodies in humans, constituting approximately 1% of circulating immunoglobulins (Galili, 2013, Immunology and Cell Biology). They specifically target the Galalpha1-3Galbeta1-4GlcNAc-R carbohydrate epitope, known as alpha-Gal, which is synthesized by the enzyme alpha-1,3-galactosyltransferase in non-primate mammals (Machado-Alba et al., 2021, Alpha-gal syndrome: A review). Because humans lack this enzyme, they produce these antibodies in response to continuous exposure to alpha-Gal epitopes on gut microbiota (Commins et al., 2011, JACI). These antibodies are the primary cause of hyperacute rejection in xenotransplantation and mediate alpha-gal syndrome, a delayed allergic reaction to red meat triggered by tick bites (Commins et al., 2011). In oncology, researchers exploit these antibodies by engineering tumor cells to express alpha-Gal, recruiting the patient's own anti-Gal antibodies to induce immune-mediated destruction of the cancer (Galili, 2013). Conversely, drugs like Cetuximab can trigger severe hypersensitivity reactions in individuals with pre-existing anti-Gal IgE antibodies (Chung et al., 2008, NEJM).

Other names

Anti-Gal antibodyAnti-alpha-galactosyl antibodyAnti-alpha-Gal IgGAnti-alpha-Gal IgMAnti-alpha-Gal IgE

Binding to alpha-Gal epitopes on foreign tissues, bioprosthetics, or drugs, leading to complement-mediated lysis, antibody-dependent cellular cytotoxicity (ADCC), or anaphylaxis; therapeutic strategies involve either neutralizing these antibodies using decoys or utilizing them to target alpha-Gal-expressing tumors for destruction.