{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T12:19:16Z","timestamp":1787746756687,"version":"build-2784847793"},"reference-count":73,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T00:00:00Z","timestamp":1787702400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Long-term immunosuppressant use after solid organ transplantation causes serious complications, including chronic rejection, infection, malignancy, and metabolic disorders, which has motivated the clinical pursuit of immune tolerance induction. Sequential antibody induction protocols \u2013 using peri-transplant antibodies (e.g., alemtuzumab, anti-thymocyte globulin, belatacept, anti-CD40 monoclonal antibodies) combined with phased reduction or withdrawal of maintenance drugs \u2013 aim to establish \u201coperational tolerance\u201d or complete tolerance. This review systematically examines the immunological rationale and major clinical strategies (T-cell depletion, costimulation blockade, mixed chimerism, and regulatory cell therapy). Based on efficacy, safety, and feasibility, we propose four novel sequential regimens with explicit evidence levels. Our multidimensional feasibility assessment \u2013 covering cost, complexity, risk\u2013benefit, patient selection, and regulatory barriers \u2013 indicates that costimulation-blockade protocols currently offer the best balance for near-term clinical use, whereas chimerism approaches are the most effective but remain restricted to specialised centres. Future work should integrate precise immune stratification, advanced antibody engineering, and cell-based therapies to facilitate individualized sequential protocols, ultimately moving the field from lifelong immunosuppression to controlled immune tolerance.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1900794","type":"journal-article","created":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T11:26:05Z","timestamp":1787743565000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Sequential antibody induction for immune tolerance in clinical organ transplantation: a feasibility review of immunosuppressant withdrawal protocols"],"prefix":"10.3389","volume":"17","author":[{"given":"Yachao","family":"Li","sequence":"first","affiliation":[{"name":"College of Medicine and Life Sciences, Chengdu University of Traditional Chinese Medicine","place":["Chengdu, 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