Enhancement of Autologous Tumor Vaccine Immunogenicity by Anti-Gal

Abstract

Anti-Gal is considered to be the most prevalent naturally occurring antibody common to all humans. It represents approximately 1 % of total IgG in the serum in humans and interacts specifically with the α-gal epitope of cell surface glycoproteins and glycolipids (see the chapter on “The Natural Anti-Gal Antibody” Galili, 1993; Galili et al., 1985; Galili et al., 1984). Understandably, the α-gal epitope is not expressed on tissues or cells derived from human sources since the enzyme synthesizing this epitope, the α 1,3 galactosyltransferase, is not active in humans (see the chapter on “Evolution of α 1,3 Galactosyltransferase and the α-Gal Epitope” Galili et al., 1988). But imagine the consequences of a human cell genetically or enzymatically engineered to express the α-gal epitope on its surface and then introduced into a normal individual. A prediction of the outcome lies in studies in xenotransplantation where non-primate mammalian tissues, which normally express the α-gal epitope, succumb to hyperacute immune rejection when trans- planted into a human recipient (see the chapter ofKobayashi and Cooper on “AntiGal in Xenotransplantation” Collins et al., 1994; Galili 1993b; Sandrin et al., 1993; Good et al., 1992). Anti-Gal thus forms an immunological barrier preventing xenotransplantation facilitated by binding to a-gal epitopes on the surface of the xenograft. Both IgM and IgG isotypes of anti-Gal bind the a-gal epitopes on the xenograft and destroy it through antibody mediated effector mechanisms such as antibody dependent cell cytotoxicity (ADCC) and complement fixation and lysis (Galili 1993b; Sandrin et al., 1993; Good et al., 1992).