Minnelide suppresses GVHD and enhances survival while maintaining GVT responses

• DOI: 10.1172/jci.insight.165936
• Publication Date: 2024-04-11T16:00:22Z
• Authors: Sabrina N. Copsel; Vanessa T. Garrido; Henry Barreras; Cameron S. Bader; Brent Pfeiffer; Beatriz Mateo-Vic...; Dietlinde Wolf; Miguel Gallardo; Sophie Paczesny; Krishna V. Komanduri; Cara L. Benjamin; Alejandro V. Vill...; Ashok K. Saluja; Robert B. Levy
• Keywords: Triptolide

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 triptolide, has demonstrated potent antiinflammatory antitumor activity in several preclinical models proven both safe efficacious clinical trials for advanced gastrointestinal malignancies. Here, we tested effectiveness Minnelide preventing acute GVHD as compared posttransplant cyclophosphamide (PTCy). Strikingly, found improved survival, weight loss, scores an MHC-mismatched model aHSCT. These were also apparent minor MHC-matched xenogeneic HSCT models. was comparable to PTCy terms score, colonic length. Notably, addition decreased donor T infiltration early after aHSCT, regulatory populations, including Tregs, ILC2s, myeloid-derived cells colon increased, which together may account Minnelide's suppression Importantly, prevention accompanied preservation graft-versus-tumor activity. As possesses anti-acute myeloid leukemia (anti-AML) is being applied trials, present findings, conclude that this compound might provide new approach AML undergoing