PubMed · 2264530
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R Hong. 1990. Transplantation immunity: basic principles and future projections.. https://pubmed.ncbi.nlm.nih.gov/2264530/
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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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The aim of this study was to compare two different periods of tacrolimus rescue therapy for intractable rejection. From January 1992 to May 1996, 140 liver transplants (LTx) were performed in our hospital under cyclosporine A-based immunosuppression. Twenty-four (17.1%) patients were switched to tacrolimus because of chronic rejection, steroid-resistant rejection or cholestasic hepatitis C recurrence. Mean follow-up was 21 months (range 12-56 months). In the first period (January 1992-March 1994), conversion to tacrolimus was indicated later, after unsuccessful repeated rejection therapy. In the second period (April 1994-May 1996), conversion to tacrolimus was indicated early, immediately after unsuccessful rejection therapy or directly at the moment of diagnosis with no further treatment. Eleven of 54 LTx were treated with tacrolimus in period 1 (20.3%), and 13 of 86 LTx in period 2 (15.1%). Only 4 of 11 (36.6%) grafts converted were rescued during the first period, while 11 of 13 (84.6%) were rescued in the second (P < 0.03). Patients in the first period received more courses of steroids than those of the second (1.7 +/- 0.7 vs 0.9 +/- 0.7, P < 0.02). Furthermore, six patients received one or two courses of OKT3 in period 1 while only one received one course in period 2 (P < 0.03). Preconversion mean bilirubin levels of patients in the first period were higher than those in the second (15.9 +/- 7.3 mg/dl vs 9.7 +/- 5.8 mg/dl, P < 0.05). Preconversion mean bilirubin levels of 6.8 +/- 5.4 mg/dl and 21.8 +/- 18.5 mg/dl were observed in patients with successful and unsuccessful tacrolimus rescue therapy, respectively, independent of the treatment period (P < 0.05). Mortality rates were higher in the first period than in the second (82% versus 23%; P < 0.02). In conclusion, conversion to tacrolimus as rescue therapy for intractable rejection or cholestasic hepatitis C recurrence is an efficacious alternative, particularly when tacrolimus is initiated early.