The problem of anti-pig antibodies in pig-to-primate xenografting: current and novel methods of depletion and/or suppression of production of anti-pig antibodies

The role of antibodies directed against Gal alpha l-3Gal (alpha-Gal) epitopes in porcine-to-primate xenotransplantation has been widely studied during the past few years. These antibodies (anti-alpha-Gal) have been associated with both hyperacute rejection and acute vascular rejection of vascularized organs. Depletion and (temporary or permanent) suppression of production of anti-alpha-Gal seem to be essential to the long-term survival of these organs, even when the ultimate aim is accommodation or tolerance. Although more than 95% depletion of anti-alpha-Gal can be achieved by the use of immunoaffinity column technology, to date no regimen has been successful in preventing the return of anti-alpha-Gal (from continuing production). In this review, we discuss current and novel methods for achieving depletion or inhibition (i.e. extracorporeal immunoadsorption, anti-idiotypic antibodies, the intravenous infusion of immunoglobulin or oligosaccharides) and suppression of production (i.e. irradiation, pharmacologic agents, specific monoclonal antibodies, immunotoxins) of anti-alpha-Gal antibodies.