ArticleAmerican journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons2013
Belatacept and sirolimus prolong nonhuman primate renal allograft survival without a requirement for memory T cell depletion.
Article in American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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The trial behind it
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Who cites it
39 citing papers in PubMed, 68 citations in OpenAlex.
- mTOR Inhibitor Therapy Diminishes Circulating CD8+ CD28- Effector Memory T Cells and Improves Allograft Inflammation in Belatacept-refractory Renal Allograft Rejection.Transplantation · 2020Trial
- A review of immunosuppressive therapy in the context of uterine VCA and pregnancy.Frontiers in transplantation · 2026Review
- Donor-specific mesenchymal stem cell infusion in human and nonhuman primate kidney transplantation.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2025Article
- Belatacept and non-melanoma skin cancer risk in kidney transplant recipients: a narrative review from a mechanistic and clinical perspective.BMC nephrology · 2025Review
- Tolerance Induction Strategies in Organ Transplantation: Current Status and Future Perspectives.Transplant international : official journal of the European Society for Organ Transplantation · 2025Review
- Consistent survival in consecutive cases of life-supporting porcine kidney xenotransplantation using 10GE source pigs.Nature communications · 2024Article
- Functional Characteristics and Phenotypic Plasticity of CD57Journal of immunology (Baltimore, Md. : 1950) · 2021Article
- Secondary lymphoid tissue and costimulation-blockade resistant rejection: A nonhuman primate renal transplant study.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2019Article
- Transplant research in nonhuman primates to evaluate clinically relevant immune strategies in organ transplantation.Transplantation reviews (Orlando, Fla.) · 2019Review
- Corticosteroids and methotrexate as adjuvants to costimulation blockade in non-human primate renal transplantation.Clinical transplantation · 2019Article
- High Dimensional Renal Profiling: Towards a Better Understanding or Renal Transplant Immune Suppression.Current transplantation reports · 2019Article
- Memory T cells are significantly increased in rejected liver allografts of rhesus monkeys.Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society · 2018Article
- T Cell Repertoire Maturation Induced by Persistent and Latent Viral Infection Is Insufficient to Induce Costimulation Blockade Resistant Organ Allograft Rejection in Mice.Frontiers in immunology · 2018Article
- Selective Targeting of High-Affinity LFA-1 Does Not Augment Costimulation Blockade in a Nonhuman Primate Renal Transplantation Model.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2017Article
- Belatacept: the challenges with transformational drugs.Translational andrology and urology · 2017Article
- The Knife's Edge of Tolerance: Inducing Stable Multilineage Mixed Chimerism but With a Significant Risk of CMV Reactivation and Disease in Rhesus Macaques.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2017Article
- The Role of Costimulation Blockade in Solid Organ and Islet Xenotransplantation.Journal of immunology research · 2017Review
- Impact of Immune-Modulatory Drugs on Regulatory T Cell.Transplantation · 2016Review
- Review
- Novel surgical techniques, regenerative medicine, tissue engineering and innovative immunosuppression in kidney transplantation.Archives of medical science : AMS · 2016Article
Corrections and comments
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
Abstract
Belatacept is an inhibitor of CD28/B7 costimulation that is clinically indicated as a calcineurin inhibitor (CNI) alternative in combination with mycophenolate mofetil and steroids after renal transplantation. We sought to develop a clinically translatable, nonlymphocyte depleting, belatacept-based regimen that could obviate the need for both CNIs and steroids. Thus, based on murine data showing synergy between costimulation blockade and mTOR inhibition, we studied rhesus monkeys undergoing MHC-mismatched renal allotransplants treated with belatacept and the mTOR inhibitor, sirolimus. To extend prior work on costimulation blockade-resistant rejection, some animals also received CD2 blockade with alefacept (LFA3-Ig). Belatacept and sirolimus therapy successfully prevented rejection in all animals. Tolerance was not induced, as animals rejected after withdrawal of therapy. The regimen did not deplete T cells. Alefecept did not add a survival benefit to the optimized belatacept and sirolimus regimen, despite causing an intended depletion of memory T cells, and caused a marked reduction in regulatory T cells. Furthermore, alefacept-treated animals had a significantly increased incidence of CMV reactivation, suggesting that this combination overly compromised protective immunity. These data support belatacept and sirolimus as a clinically translatable, nondepleting, CNI-free, steroid-sparing immunomodulatory regimen that promotes sustained rejection-free allograft survival after renal transplantation.
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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.