ArticleFrontiers in immunology2017
Targeting the Human T-Cell Inducible COStimulator Molecule with a Monoclonal Antibody Prevents Graft-vs-Host Disease and Preserves Graft vs Leukemia in a Xenograft Murine Model.
Article in Frontiers in immunology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 28 citations in OpenAlex.
- Pathophysiology and preclinical relevance of experimental graft-versus-host disease in humanized mice.Biomarker research · 2024Review
- High dimensional proteomic mapping of bone marrow immune characteristics in immune thrombocytopenia.Science China. Life sciences · 2024Article
- Comprehensive analysis of the role of ICOS ( CD278 ) in pan-cancer prognosis and immunotherapy.BMC cancer · 2023Article
- Insights into mechanisms of graft-versus-host disease through humanised mouse models.Bioscience reports · 2022Review
- Mice with humanized immune system as novel models to study HIV-associated pulmonary hypertension.Frontiers in immunology · 2022Article
- Change in Programmed Death-1 and Inducible Costimulator Expression in Patients whit Acute Myeloid Leukemia Following Chemotherapy and Its Cytogenetic Abnormalities : Change in PD-1 and ICOS Expression in Patients whit AML.Galen medical journal · 2022Article
- Cytotoxic T lymphocyte antigen-4 regulates development of xenogenic graft versus host disease in mice via modulation of host immune responses induced by changes in human T cell engraftment and gene expression.Clinical and experimental immunology · 2021Article
- Daratumumab Prevents Experimental Xenogeneic Graft-Versus-Host Disease by Skewing Proportions of T Cell Functional Subsets and Inhibiting T Cell Activation and Migration.Frontiers in immunology · 2021Article
- GVHD Pathogenesis, Prevention and Treatment: Lessons From Humanized Mouse Transplant Models.Frontiers in immunology · 2021Review
- Targeting co-stimulatory molecules in autoimmune disease.Nature reviews. Drug discovery · 2020Review
- Cellular and molecular profiling of T-cell subsets at the onset of human acute GVHD.Blood advances · 2020Article
- Bendamustine with total body irradiation conditioning yields tolerant T-cells while preserving T-cell-dependent graft-versus-leukemia.Oncoimmunology · 2020Article
- Human Apoptotic Cells, Generated by Extracorporeal Photopheresis, Modulate Allogeneic Immune Response.Frontiers in immunology · 2019Article
- Antitumor activity of EGFR-specific CAR T cells against non-small-cell lung cancer cells in vitro and in mice.Cell death & disease · 2018Article
- Xenogeneic Graft-Versus-Host Disease in Humanized NSG and NSG-HLA-A2/HHD Mice.Frontiers in immunology · 2018Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundGraft-vs-host disease (GVHD) is a major complication of allogenic bone marrow transplantation (BMT). Targeting costimulatory molecules with antagonist antibodies could dampen the excessive immune response that occurs, while preserving the beneficial graft vs leukemia (GVL) of the allogeneic response. Previous studies using a mouse model of GVHD have shown that targeting the T-cell Inducible COStimulator (ICOS, CD278) molecule is beneficial, but it is unclear whether the same applies to human cells.
methodsHere, we assessed whether a monoclonal antibody (mAb) to human ICOS was able to antagonize the costimulatory signal delivered
resultsIn this model, control mice invariably lost weight and died by day 50. In contrast, 65% of the mice receiving a single injection of the anti-hICOS mAb survived beyond 100 days. Moreover, a significant improvement in survival was obtained in a curative xeno-GVHD setting. Mechanistically, administration of the anti-hICOS mAb was associated with a strong reduction in perivascular infiltrates in liver and lungs and reduction in frequencies and numbers of human T cells in the spleen. In addition, the mAb prevented T-cell expansion in the blood during xeno-GVHD. Importantly, GVHD-protected mice retained the ability to control the P815 mastocytoma cell line, mimicking GVL in humans.
conclusionA mAb-targeting human ICOS alleviated GVHD without impairing GVL in a xenograft murine model. Thus, ICOS represents a promising target in the management of BMT, preventing GVHD while preserving GVL.
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