PubMed · 11118106
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S Sudhindran, N Emms, S Sinha, A Kumar. 2000-11-27. Too many confounding variables.. https://doi.org/10.1097/00007890-200011270-00027
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The growing gap between organ demand and clinical availability has renewed interest in immune-evasive graft strategies, yet rejection and lifelong immunosuppression remain major barriers to durable success. Advances in genome editing enable immune-evasive cell platforms designed to avoid immune recognition while replacing missing function in allogeneic settings. This review summarizes current strategies for engineering immune-evasive grafts that simultaneously suppress adaptive and innate immune responses. We discuss how coordinated modulation of antigen presentation and immune checkpoint pathways can protect transplanted allogeneic cells and tissues from T, NK, and macrophage-mediated rejection. We also present the emerging concept of integrating hypoimmune engineering with genetically modified porcine donors, where extensive genome editing has reduced, but not eliminated, xenogeneic immune barriers. Combining donor genome modification with immune-evasive graft design represents a promising conceptual advance toward xenograft survival, though whether full elimination of systemic immunosuppression is achievable remains to be established clinically. We further examine how the regulatory landscape for these products is evolving across major jurisdictions, and how differences in approval pathways, manufacturing standards, and long-term surveillance requirements shape the path to clinical translation. Finally, we outline the safety considerations and remaining limitations in immune evasion that must be addressed to enable clinical implementation.
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In the period 1996-2001, the number of transplanted postmortal kidneys decreased from 425 to 380, while at the same time the number of kidneys transplanted from living donors increased from 81 in 1996 to 155 per year in 2001. There was a striking increase in the proportion of living non-related donors (59/155). Although the short-term results of kidney transplantation have improved, and kidneys are very rarely lost as a consequence of acute rejection, the average life of a transplanted kidney has scarcely improved. Chronic allograft dysfunction is now the major cause of transplant loss. This process is hardly influenced by the immunosuppressive drugs currently used. To improve the cardiovascular risk profile, several centres discontinue the use of cyclosporin, tacrolimus or prednisone at 6 or 12 months after transplantation or substitute these with other drugs. This is complicated by acute rejection episodes in 10-20% of patients. With the arrival of a number of new immunosuppressive drugs the risk of rejection might be reduced.