Edwin Emilio Valdivia Malqui Gene therapy: decreasing MHC expression of cells, organs and beyond Allogeneic transplantation is the only way to replace non-functioning organs, but access to transplants is limited by the shortage of donor organs and immunological mismatches between the donor and the recipient. Despite the fact that immunosuppressive therapy can reduce the risk of rejection related to these discrepancies, chronic rejection is still a great hurdle to long-term graft survival. Major

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... histocompatibility complex (MHC) molecules are key players in allograft recognition and rejection. They trigger both cellular and humoral immune responses through direct, indirect and semi-direct allorecognition pathways. To decrease the probabilities of rejection, donors and recipients are paired based on their MHC genotype. Nevertheless, a fully matched pair is unlikely because the MHC gene is highly polymorphic. Mismatches between donor and recipient MHC genotypes are responsible for triggering potent allogeneic humoral and cellular immune responses, which lead to allograft rejection. Immunosuppressive drugs controls allograft rejection to a certain extent by various mechanisms, for example, by blocking immune cells proliferation (e.g., tacrolimus and cyclosporine) or by inhibiting the production of cytokines or cytokine receptors (e.g., basiliximab, tofacitinib). However, this type of therapy must be taken lifelong and because of their general inhibition of immune responses, it reduces the capacity of the recipient's immune system to recognize and eliminate pathogens or cancer cells.