ArticleThe Journal of clinical investigation2018
CD28 blockade controls T cell activation to prevent graft-versus-host disease in primates.
Article in The Journal of clinical investigation, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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
37 citing papers in PubMed, 56 citations in OpenAlex.
- Genetically engineered porcine liver: a new era in transplantation.International journal of surgery (London, England) · 2026Article
- Targeting Aurora kinase A to prevent GVHD and relapse after myeloablative allogeneic hematopoietic cell transplantation.Blood advances · 2026Article
- Abatacept improves posttransplant survival and reduces endothelial injury syndromes in β-thalassemia major.Blood advances · 2025Article
- New age GVHD prophylaxis regimens: what works for what donor and why.Hematology. American Society of Hematology. Education Program · 2025Review
- Article
- Organ-specific microenvironments drive divergent T cell evolution in acute graft-versus-host disease.Science translational medicine · 2025Article
- Article
- CD70 identifies alloreactive T cells and represents a potential target for prevention and treatment of acute GVHD.Blood advances · 2024Article
- Major breakthroughs in hematopoietic stem cell transplantation and future challenges in clinical implementation.The Journal of clinical investigation · 2024Article
- CRISPR/Cas9 deletion of MIR155HG in human T cells reduces incidence and severity of acute GVHD in a xenogeneic model.Blood advances · 2024Article
- Chronic GvHD NIH Consensus Project Biology Task Force: evolving path to personalized treatment of chronic GvHD.Blood advances · 2023Article
- Notch signaling drives intestinal graft-versus-host disease in mice and nonhuman primates.Science translational medicine · 2023Article
- Facing challenges with hope: universal immune cells for hematologic malignancies.Cancer biology & medicine · 2023Review
- Lkb1 loss in regulatory T cells leads to dysregulation of hematopoietic stem cell expansion and differentiation in bone marrow.FEBS open bio · 2023Article
- Targeting immune checkpoints in anti-neutrophil cytoplasmic antibodies associated vasculitis: the potential therapeutic targets in the future.Frontiers in immunology · 2023Review
- Fibroblastic reticular cells mitigate acute GvHD via MHCII-dependent maintenance of regulatory T cells.JCI insight · 2022Article
- Costimulation blockade in combination with IL-2 permits regulatory T cell sparing immunomodulation that inhibits autoimmunity.Nature communications · 2022Article
- Steroid-Refractory Gut Graft-Versus-Host Disease: What We Have Learned From Basic Immunology and Experimental Mouse Model.Frontiers in immunology · 2022Review
- Milestones in acute GVHD pathophysiology.Frontiers in immunology · 2022Review
- Insights from integrating clinical and preclinical studies advance understanding of graft-versus-host disease.The Journal of clinical investigation · 2021Review
Corrections and comments
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Authors and funding
24 authors at 5 institutions in 2 countries.
Funding
Abstract
Controlling graft-versus-host disease (GVHD) remains a major unmet need in stem cell transplantation, and new, targeted therapies are being actively developed. CD28-CD80/86 costimulation blockade represents a promising strategy, but targeting CD80/CD86 with CTLA4-Ig may be associated with undesired blockade of coinhibitory pathways. In contrast, targeted blockade of CD28 exclusively inhibits T cell costimulation and may more potently prevent GVHD. Here, we investigated FR104, an antagonistic CD28-specific pegylated-Fab', in the nonhuman primate (NHP) GVHD model and completed a multiparameter interrogation comparing it with CTLA4-Ig, with and without sirolimus, including clinical, histopathologic, flow cytometric, and transcriptomic analyses. We document that FR104 monoprophylaxis and combined prophylaxis with FR104/sirolimus led to enhanced control of effector T cell proliferation and activation compared with the use of CTLA4-Ig or CTLA4-Ig/sirolimus. Importantly, FR104/sirolimus did not lead to a beneficial impact on Treg reconstitution or homeostasis, consistent with control of conventional T cell activation and IL-2 production needed to support Tregs. While FR104/sirolimus had a salutary effect on GVHD-free survival, overall survival was not improved, due to death in the absence of GVHD in several FR104/sirolimus recipients in the setting of sepsis and a paralyzed INF-γ response. These results therefore suggest that effectively deploying CD28 in the clinic will require close scrutiny of both the benefits and risks of extensively abrogating conventional T cell activation after transplant.
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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.