دورية أكاديمية
Minnelide suppresses GVHD and enhances survival while maintaining GVT responses.
| العنوان: | Minnelide suppresses GVHD and enhances survival while maintaining GVT responses. |
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| المؤلفون: | Copsel SN; Department of Microbiology and Immunology., Garrido VT; Department of Surgery, and., Barreras H; Department of Microbiology and Immunology., Bader CS; Department of Microbiology and Immunology., Pfeiffer B; Department of Pediatrics, University of Miami, Miller School of Medicine, Miami, Florida, USA., Mateo-Victoriano B; Department of Surgery, and., Wolf D; Sylvester Comprehensive Cancer Center., Gallardo M; Department of Microbiology and Immunology., Paczesny S; Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, South Carolina, USA., Komanduri KV; Department of Microbiology and Immunology.; Sylvester Comprehensive Cancer Center.; Department of Medicine, and., Benjamin CL; Sylvester Comprehensive Cancer Center.; Department of Medicine, and., Villarino AV; Department of Microbiology and Immunology., Saluja AK; Department of Surgery, and.; Sylvester Comprehensive Cancer Center., Levy RB; Department of Microbiology and Immunology.; Sylvester Comprehensive Cancer Center.; Department of Ophthalmology, University of Miami, Miller School of Medicine, Miami, Florida, USA. |
| المصدر: | JCI insight [JCI Insight] 2024 Apr 11; Vol. 9 (9). Date of Electronic Publication: 2024 Apr 11. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't; Research Support, N.I.H., Extramural |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Society for Clinical Investigation Country of Publication: United States NLM ID: 101676073 Publication Model: Electronic Cited Medium: Internet ISSN: 2379-3708 (Electronic) Linking ISSN: 23793708 NLM ISO Abbreviation: JCI Insight Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Ann Arbor, Michigan : American Society for Clinical Investigation, [2016]- |
| مواضيع طبية MeSH: | Graft vs Host Disease*/prevention & control , Graft vs Host Disease*/drug therapy , Hematopoietic Stem Cell Transplantation*/methods , Diterpenes*/pharmacology , Diterpenes*/therapeutic use , Epoxy Compounds*/pharmacology , Epoxy Compounds*/therapeutic use , Phenanthrenes*/pharmacology , Phenanthrenes*/therapeutic use, Animals ; Mice ; Humans ; Transplantation, Homologous ; Female ; Cyclophosphamide/pharmacology ; Cyclophosphamide/therapeutic use ; Disease Models, Animal ; Graft vs Leukemia Effect/drug effects ; Mice, Inbred C57BL ; Male |
| مستخلص: | Allogeneic hematopoietic stem cell transplantation (aHSCT) can cure patients with otherwise fatal leukemias and lymphomas. However, the benefits of aHSCT are limited by graft-versus-host disease (GVHD). Minnelide, a water-soluble analog of triptolide, has demonstrated potent antiinflammatory and antitumor activity in several preclinical models and has proven both safe and efficacious in clinical trials for advanced gastrointestinal malignancies. Here, we tested the effectiveness of Minnelide in preventing acute GVHD as compared with posttransplant cyclophosphamide (PTCy). Strikingly, we found Minnelide improved survival, weight loss, and clinical scores in an MHC-mismatched model of aHSCT. These benefits were also apparent in minor MHC-matched aHSCT and xenogeneic HSCT models. Minnelide was comparable to PTCy in terms of survival, GVHD clinical score, and colonic length. Notably, in addition to decreased donor T cell infiltration early after aHSCT, several regulatory cell populations, including Tregs, ILC2s, and myeloid-derived stem cells in the colon were increased, which together may account for Minnelide's GVHD suppression after aHSCT. Importantly, Minnelide's GVHD prevention was accompanied by preservation of graft-versus-tumor activity. As Minnelide possesses anti-acute myeloid leukemia (anti-AML) activity and is being applied in clinical trials, together with the present findings, we conclude that this compound might provide a new approach for patients with AML undergoing aHSCT. |
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| معلومات مُعتمدة: | R01 EY030283 United States EY NEI NIH HHS; R41 AI149916 United States AI NIAID NIH HHS; F99 CA245728 United States CA NCI NIH HHS; K00 CA245728 United States CA NCI NIH HHS; R01 CA168814 United States CA NCI NIH HHS |
| فهرسة مساهمة: | Keywords: Cellular immune response; Immunology; Stem cell transplantation; Transplantation |
| المشرفين على المادة: | 0 (Diterpenes) 0 (Epoxy Compounds) 0 (Phenanthrenes) 19ALD1S53J (triptolide) 8N3DW7272P (Cyclophosphamide) |
| تواريخ الأحداث: | Date Created: 20240411 Date Completed: 20240508 Latest Revision: 20240603 |
| رمز التحديث: | 20240603 |
| مُعرف محوري في PubMed: | PMC11141936 |
| DOI: | 10.1172/jci.insight.165936 |
| PMID: | 38602775 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 2379-3708 |
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| DOI: | 10.1172/jci.insight.165936 |