ArticleJCI insight2017
Interruption of OX40L signaling prevents costimulation blockade-resistant allograft rejection.
Article in JCI insight, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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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
13 citing papers in PubMed.
- CAR T cell therapy beyond cancer: current status, challenges and future prospects.Signal transduction and targeted therapy · 2026Review
- Best practices in mouse models of skin transplantation.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2026Review
- A review of immunosuppressive therapy in the context of uterine VCA and pregnancy.Frontiers in transplantation · 2026Review
- Article
- Tolerogenic Therapies in Cardiac Transplantation.International journal of molecular sciences · 2025Review
- Tolerance Induction Strategies in Organ Transplantation: Current Status and Future Perspectives.Transplant international : official journal of the European Society for Organ Transplantation · 2025Review
- Rapamycin Prevents Expansion of Costimulation Blockade-resistant CD8+ Alloreactive Memory Cells following Depletional Induction in Renal Transplant Recipients.Journal of immunology (Baltimore, Md. : 1950) · 2024Article
- Human OX40L-CAR-TScience translational medicine · 2024Article
- Clinical application of immune repertoire sequencing in solid organ transplant.Frontiers in immunology · 2023Review
- Therapeutic targeting miR130b counteracts diffuse large B-cell lymphoma progression via OX40/OX40L-mediated interaction with Th17 cells.Signal transduction and targeted therapy · 2022Article
- The past, present, and future of costimulation blockade in organ transplantation.Current opinion in organ transplantation · 2019Review
- Transplant research in nonhuman primates to evaluate clinically relevant immune strategies in organ transplantation.Transplantation reviews (Orlando, Fla.) · 2019Review
- Combined OX40L and mTOR blockade controls effector T cell activation while preserving TScience translational medicine · 2017Article
Corrections and comments
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Authors and funding
9 authors.
Funding
Abstract
The potential of costimulation blockade to serve as a novel transplant immunosuppression strategy has been explored for over 20 years, culminating in the recent clinical approval of belatacept for renal transplant patients. Despite improving long-term graft function and survival compared with calcineurin inhibitors, clinical acceptance of belatacept has been hindered by elevated rates of acute rejection. We examined the signaling pathways required to activate costimulation blockade-resistant alloreactive T cells and identified the OX40/OX40L secondary costimulatory pathway as a promising target. We next sought to improve the clinical efficacy of traditional costimulation blockade using belatacept by coupling it with anti-OX40L. Using a murine transplant model, we demonstrate that combined blockade enhances the suppression of alloreactive T cell proliferation and effector functions including both cytokine release and cytotoxic degranulation. We also show that anti-OX40L may be particularly useful in targeting alloreactive memory T cell responses that are relatively unaffected by traditional costimulation blockade regimens. Finally, we translated this therapy to a clinically relevant nonhuman primate renal transplant model, validating the efficacy of this regimen in a potentially novel steroid- and calcineurin inhibitor-free immunosuppression regimen.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.