{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,7]],"date-time":"2026-11-07T05:27:17Z","timestamp":1794029237331,"version":"4.8.0"},"reference-count":72,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,6,6]],"date-time":"2025-06-06T00:00:00Z","timestamp":1749168000000},"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:sec><jats:title>Background and Objectives<\/jats:title><jats:p>Myasthenia gravis (MG) is a T cell-dependent, B cell-mediated autoimmune disease targeting the acetylcholine receptor (AChR) and other proteins of the neuromuscular junction postsynaptic membrane. Production of pathogenic autoantibodies results from B cell activation and expansion of antibody-secreting cells, including plasma cells, whose differentiation and survival are reliant on the TNF family cytokines APRIL and BAFF. Povetacicept (ALPN-303; TACI vTD-Fc) is an Fc fusion protein of an engineered TACI domain with significantly more potent dual inhibition of APRIL and BAFF than wild-type (WT) TACI-Fc (e.g., telitacicept).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In this study, the activity of povetacicept was evaluated in the mouse experimental autoimmune MG (EAMG) model, compared to (i) telitacicept, (ii) a depleting anti-CD20 antibody, (iii) neonatal Fc receptor blocker efgartigimod, (iv) a matched Fc control protein, and (v) PBS as vehicle.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Therapeutic administration of povetacicept ameliorated clinical manifestations in EAMG mice and was associated with significantly lower levels of immunoglobulin subclasses and anti-AChR antibody titers in serum, along with increased muscle AChR content \u2013 superior to the evaluated comparators. Povetacicept treatment also reduced the number of total B220<jats:sup>+<\/jats:sup> and Ki67<jats:sup>+<\/jats:sup> proliferating cells in draining lymph node follicles and resulted in modifications of splenic T and B cell subset frequencies, compared to controls.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>The potent, dual BAFF\/APRIL inhibitor povetacicept significantly improves clinical disease activity in EAMG, associated with reductions in pathogenic anti-AChR autoantibodies and superior to comparator therapeutic interventions based on WT TACI-Fc, CD20 depletion, or FcRn inhibition. Povetacicept may therefore confer beneficial clinical outcomes in the treatment of MG and other autoantibody-related neurological diseases.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2025.1533093","type":"journal-article","created":{"date-parts":[[2025,6,6]],"date-time":"2025-06-06T09:51:22Z","timestamp":1749203482000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Povetacicept (ALPN-303; TACI vTD-Fc), an enhanced, potent dual inhibitor of BAFF and APRIL, ameliorates experimental autoimmune myasthenia gravis in C57BL\/6N 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