ArticleAmerican journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons2019
Dual targeting: Combining costimulation blockade and bortezomib to permit kidney transplantation in sensitized recipients.
Article in American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 73 citations in OpenAlex.
- Review
- The roles of the ubiquitin-proteasome system in renal disease.International journal of medical sciences · 2025Review
- Belatacept in Kidney Transplantation: Reflecting on the Past, Shaping the Future.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
- Prolonged xenokidney graft survival in sensitized NHP recipients by expression of multiple human transgenes in a triple knockout pig.Science translational medicine · 2024Article
- Costimulatory Blockade and Solid Organ Transplantation: The Past, Present, and Future.Kidney international reports · 2023Review
- Desensitization and belatacept-based maintenance therapy in pregnancy-sensitized monkeys receiving a kidney transplant.Science advances · 2023Article
- Belatacept and carfilzomib-based treatment for antibody-mediated rejection in a sensitized nonhuman primate kidney transplantation model.Frontiers in transplantation · 2023Article
- Translation of therapeutic strategies to modulate B cell reponses from non-human primate models to human kidney transplantation.Frontiers in transplantation · 2023Article
- From bench to bedside: reversing established antibody responses and desensitization.Current opinion in organ transplantation · 2022Review
- Harnessing the B Cell Response in Kidney Transplantation - Current State and Future Directions.Frontiers in immunology · 2022Review
- Targeting T Follicular Helper Cells to Control Humoral Allogeneic Immunity.Transplantation · 2021Review
- C3 complement inhibition prevents antibody-mediated rejection and prolongs renal allograft survival in sensitized non-human primates.Nature communications · 2021Article
- Optimal Immunosuppression Strategy in the Sensitized Kidney Transplant Recipient.Journal of clinical medicine · 2021Review
- Superior inhibition of alloantibody responses with selective CD28 blockade is CTLA-4 dependent and T follicular helper cell specific.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2021Article
- Therapies for Chronic Allograft Rejection.Frontiers in pharmacology · 2021Review
- Emerging New Approaches in Desensitization: Targeted Therapies for HLA Sensitization.Frontiers in immunology · 2021Review
- Approaches for Controlling Antibody-Mediated Allograft Rejection Through Targeting B Cells.Frontiers in immunology · 2021Review
- Current Desensitization Strategies in Heart Transplantation.Frontiers in immunology · 2021Review
- Approaches to Establishing Tolerance in Immune Mediated Diseases.Frontiers in immunology · 2021Review
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 2 countries.
Funding
Abstract
Previous evidence suggests that a homeostatic germinal center (GC) response may limit bortezomib desensitization therapy. We evaluated the combination of costimulation blockade with bortezomib in a sensitized non-human primate kidney transplant model. Sensitized animals were treated with bortezomib, belatacept, and anti-CD40 mAb twice weekly for a month (n = 6) and compared to control animals (n = 7). Desensitization therapy-mediated DSA reductions approached statistical significance (P = .07) and significantly diminished bone marrow PCs, lymph node follicular helper T cells, and memory B cell proliferation. Graft survival was prolonged in the desensitization group (P = .073). All control animals (n = 6) experienced graft loss due to antibody-mediated rejection (AMR) after kidney transplantation, compared to one desensitized animal (1/5). Overall, histological AMR scores were significantly lower in the treatment group (n = 5) compared to control (P = .020). However, CMV disease was common in the desensitized group (3/5). Desensitized animals were sacrificed after long-term follow-up with functioning grafts. Dual targeting of both plasma cells and upstream GC responses successfully prolongs graft survival in a sensitized NHP model despite significant infectious complications and drug toxicity. Further work is planned to dissect underlying mechanisms, and explore safety concerns.
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Registered trials
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