ResearchIn-Press PreviewImmunologyTransplantation Open Access | 10.1172/jci.insight.165936
1Microbiology and Immunology, University of Miami, Miller School of Medicine, Miami, United States of America
2Surgery, University of Miami, Miller School of Medicine, Miami, United States of America
3Pediatrics, University of Miami, Miller School of Medicine, Miami, United States of America
4Sylvester Comprehensive Cancer Center, Miami, United States of America
5Microbiology and Immunology, Medical University of South Carolina, Charleston, United States of America
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1Microbiology and Immunology, University of Miami, Miller School of Medicine, Miami, United States of America
2Surgery, University of Miami, Miller School of Medicine, Miami, United States of America
3Pediatrics, University of Miami, Miller School of Medicine, Miami, United States of America
4Sylvester Comprehensive Cancer Center, Miami, United States of America
5Microbiology and Immunology, Medical University of South Carolina, Charleston, United States of America
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1Microbiology and Immunology, University of Miami, Miller School of Medicine, Miami, United States of America
2Surgery, University of Miami, Miller School of Medicine, Miami, United States of America
3Pediatrics, University of Miami, Miller School of Medicine, Miami, United States of America
4Sylvester Comprehensive Cancer Center, Miami, United States of America
5Microbiology and Immunology, Medical University of South Carolina, Charleston, United States of America
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1Microbiology and Immunology, University of Miami, Miller School of Medicine, Miami, United States of America
2Surgery, University of Miami, Miller School of Medicine, Miami, United States of America
3Pediatrics, University of Miami, Miller School of Medicine, Miami, United States of America
4Sylvester Comprehensive Cancer Center, Miami, United States of America
5Microbiology and Immunology, Medical University of South Carolina, Charleston, United States of America
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1Microbiology and Immunology, University of Miami, Miller School of Medicine, Miami, United States of America
2Surgery, University of Miami, Miller School of Medicine, Miami, United States of America
3Pediatrics, University of Miami, Miller School of Medicine, Miami, United States of America
4Sylvester Comprehensive Cancer Center, Miami, United States of America
5Microbiology and Immunology, Medical University of South Carolina, Charleston, United States of America
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1Microbiology and Immunology, University of Miami, Miller School of Medicine, Miami, United States of America
2Surgery, University of Miami, Miller School of Medicine, Miami, United States of America
3Pediatrics, University of Miami, Miller School of Medicine, Miami, United States of America
4Sylvester Comprehensive Cancer Center, Miami, United States of America
5Microbiology and Immunology, Medical University of South Carolina, Charleston, United States of America
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1Microbiology and Immunology, University of Miami, Miller School of Medicine, Miami, United States of America
2Surgery, University of Miami, Miller School of Medicine, Miami, United States of America
3Pediatrics, University of Miami, Miller School of Medicine, Miami, United States of America
4Sylvester Comprehensive Cancer Center, Miami, United States of America
5Microbiology and Immunology, Medical University of South Carolina, Charleston, United States of America
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1Microbiology and Immunology, University of Miami, Miller School of Medicine, Miami, United States of America
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5Microbiology and Immunology, Medical University of South Carolina, Charleston, United States of America
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1Microbiology and Immunology, University of Miami, Miller School of Medicine, Miami, United States of America
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1Microbiology and Immunology, University of Miami, Miller School of Medicine, Miami, United States of America
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4Sylvester Comprehensive Cancer Center, Miami, United States of America
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1Microbiology and Immunology, University of Miami, Miller School of Medicine, Miami, United States of America
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Published April 11, 2024 - More info
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 anti-inflammatory and anti-tumor activity in several pre-clinical models and has proven both safe and efficacious in clinical trials for advanced gastro-intestinal malignancies. Here, we tested the effectiveness of Minnelide in preventing acute GVHD as compared to cyclophosphamide post-aHSCT (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 post-HSCT, several regulatory cell populations including Tregs, ILC2s and MDSCs in the colon were increased which together may account for Minnelide’s GVHD suppression post-HSCT. Importantly, Minnelide GVHD prevention was accompanied by preservation of graft-versus-tumor (GVT) activity. As Minnelide possesses 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 AML patients undergoing aHSCT.