Solid Organ Xenotransplantation: Experience in the Pig-to-Primate Transplantation Model

Abstract

Background: Unlike a solid organ allograft, the rejection of a solid organ porcine xenograft involves almost all branches of the immune system, and prevention or treatment of rejection appears a complicated task. Methods: Part of experience gathered in the transplantation programs at BioTransplant-USA and Novartis-Imutran-UK (founders of Immerge BioTherapeutics) will be presented, as well as potential complications in the nonhuman primate model with respect to potential extrapolation of experimental animal data to the clinical situation. Results: The major barriers in xenograft rejection are hyperacute rejection mediated by natural antibodies, followed by acute humoral and acute cellular rejection, which can require sensitization. Various aspects of the xenogeneic rejection response can be studiedin vitro orex vivo, but a final proof-of-concept in preclinical work is to come from experimental transplantation. Since natural anti-porcine carbohydrate antibodies, which form the major part of the hyperacute rejection reaction, only occur in Old-World nonhuman primates and humans, large-animal transplantation models often involve cynomolgus monkeys and baboons. Conclusions: In addition to conventional immunosuppression, animal genetic engineering and tolerance induction are presently actively pursued to obtain long-term xenograft survival in this model.