ArticleAmerican journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons2023
TNX-1500, a crystallizable fragment-modified anti-CD154 antibody, prolongs nonhuman primate cardiac allograft survival.
Article in American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
22 citing papers in PubMed, 1 synthesis or guideline pooled it, 28 citations in OpenAlex.
- Systematic Review and Comparative Outcomes Analysis of NHP Liver Allotransplants and Xenotransplants.XenotransplantationPooled it
- First-in-Human, Phase 1, Randomized, Double-Blind, Placebo-Controlled Study of TNX-1500, an Fc-Modified anti-CD154 Monoclonal Antibody, Evaluating the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single-Ascending Doses in Healthy Adults.Journal of clinical immunology · 2026Trial
- Re-engineering CD154 blockade for transplantation: Fc-free design to separate thrombotic risk from therapeutic function.Clinical transplantation and research · 2026Review
- Progress in immunological research on innate effectors in xenotransplantation.Surgery today · 2026Review
- Mechanisms of donor-specific transfusion synergy with anti-CD154 for transplant acceptance.Journal of immunology (Baltimore, Md. : 1950) · 2026Article
- Curbing Autoimmunity: A New Fab Fragment Targeting CD40-CD40L Halts B-Cell Activation and Differentiation.European journal of immunology · 2026Article
- T cell-mediated immune responses in xenotransplantation: mechanisms and therapeutic strategies.Frontiers in immunology · 2026Review
- Cell-intrinsic CD4 T cell tolerance: a new frontier in therapy?Trends in immunology · 2025Review
- Allogeneic Liver Transplantation in Nonhuman Primates: Surgical Technique With Stable Postoperative Outcomes.Transplantation direct · 2025Article
- Enhanced Costimulation Blockade With αCD154, αCD2, and αCD28 to Promote Heart Allograft Tolerance in Nonhuman Primates.Transplantation · 2025Article
- Tolerogenic Therapies in Cardiac Transplantation.International journal of molecular sciences · 2025Review
- Is there a need for an alternative source of red blood cells for clinical transfusion and will gene-edited pigs fulfil that need?Vox sanguinis · 2025Article
- Pig Lung Xenotransplantation: Barriers on the Road to Clinical Translation.Transplant international : official journal of the European Society for Organ Transplantation · 2025Review
- CD154 blockade effectively controls antibody-mediated rejection in highly sensitized nonhuman primate kidney transplant recipients.Science translational medicine · 2025Article
- Extended survival of 9- and 10-gene-edited pig heart xenografts with ischemia minimization and CD154 costimulation blockade-based immunosuppression.The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation · 2024Article
- T cell responsiveness to IL-10 defines the immunomodulatory effect of costimulation blockade via anti-CD154 and impacts transplant survival.bioRxiv : the preprint server for biology · 2024Article
- The Evolution of Immunosuppressive Therapy in Pig-to-Nonhuman Primate Organ Transplantation.Transplant international : official journal of the European Society for Organ Transplantation · 2024Review
- Small-molecule inhibitors of the CD40-CD40L costimulatory interaction are effective in pancreatic islet transplantation and prevention of type 1 diabetes models.Frontiers in immunology · 2024Article
- The anti-CD40L monoclonal antibody AT-1501 promotes islet and kidney allograft survival and function in nonhuman primates.Science translational medicine · 2023Article
- Novel factors potentially initiating acute antibody-mediated rejection in pig kidney xenografts despite an efficient immunosuppressive regimen.XenotransplantationArticle
Corrections and comments
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Authors and funding
14 authors at 5 institutions in 3 countries.
Funding
Abstract
Blockade of the CD40/CD154 T cell costimulation pathway is a promising approach to supplement or replace current clinical immunosuppression in solid organ transplantation. We evaluated the tolerability and activity of a novel humanized anti-CD154 monoclonal antibody, TNX-1500 (TNX), in a nonhuman primate heterotopic cardiac allogeneic (allo) transplant model. TNX-1500 contains a rupluzimab fragment antigen-binding region and an immunoglobin G4 crystallizable fragment region engineered to reduce binding to the crystallizable fragment gamma receptor IIa and associated risks of thrombosis. Recipients were treated for 6 months with standard-dose TNX (sTNX) monotherapy, low-dose TNX monotherapy (loTNX), or loTNX with mycophenolate mofetil (MMF) (loTNX + MMF). Results were compared with historical data using chimeric humanized 5c8 monotherapy dosed as for loTNX but discontinued at 3 months. Median survival time was similar for humanized 5c8 and both loTNX groups, but significantly longer with sTNX (>265 days) than with loTNX (99 days) or loTNX + MMF (88 days) (P < 0.05 for both comparisons against sTNX). Standard-dose TNX prevented antidonor alloantibody elaboration, inhibited chronic rejection, and was associated with a significantly reduced effector T cells/regulatory T cells ratio relative to loTNX with MMF. No thrombotic complications were observed. This study demonstrated that TNX was well tolerated, prolongs allograft survival, and prevents alloantibody production and cardiac allograft vasculopathy in a stringent preclinical nonhuman primate heart allotransplant model.
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Registered trials
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