Cord blood T regulatory cells synergize with ruxolitinib to improve GVHD outcomes
BackgroundAdoptive therapy with umbilical cord blood (UCB) T-regulatory (Treg) cells can prevent graft vs. host disease (GVHD). We hypothesize that UCB Tregs can treat GVHD and synergize with ruxolitinib, Jak2 inhibitor, to improve outcomes.MethodsUCB Treg potency and efficacy was examined using cel...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2024-12-01
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| Series: | Frontiers in Transplantation |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/frtra.2024.1448650/full |
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| author | Ke Zeng Hongbing Ma Meixian Huang Mi-Ae Lyu Tara Sadeghi Christopher R. Flowers Simrit Parmar |
| author_facet | Ke Zeng Hongbing Ma Meixian Huang Mi-Ae Lyu Tara Sadeghi Christopher R. Flowers Simrit Parmar |
| author_sort | Ke Zeng |
| collection | DOAJ |
| description | BackgroundAdoptive therapy with umbilical cord blood (UCB) T-regulatory (Treg) cells can prevent graft vs. host disease (GVHD). We hypothesize that UCB Tregs can treat GVHD and synergize with ruxolitinib, Jak2 inhibitor, to improve outcomes.MethodsUCB Treg potency and efficacy was examined using cell suppression assay and xenogeneic GVHD model, respectively. Ruxolitinib was fed continuously in presence or absence of CellTraceViolet tagged UCB Tregs on days +4, +7, +11, +18. Mice were followed for survival, GVHD score, hematology parameters and inflammation.ResultsAddition of ruxolitinib to UCB Tregs exerted synergistic suppressor function in vitro and improved persistence of UCB Tregs in vivo. Lower GVHD score, improved survival, increased hemoglobin level and platelet count, decreased inflammatory cytokines and decrease in CD3+ T cell lung infiltrate was observed in UCB Tregs+ruxolitinib recipients.ConclusionUCB Treg+Ruxolitinib combination improves outcomes in xenogeneic GVHD and should be explored in a clinical setting. |
| format | Article |
| id | doaj-art-3938738d4cd34e66a46f8d5c3ab3ddd8 |
| institution | Kabale University |
| issn | 2813-2440 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Transplantation |
| spelling | doaj-art-3938738d4cd34e66a46f8d5c3ab3ddd82024-12-11T06:44:34ZengFrontiers Media S.A.Frontiers in Transplantation2813-24402024-12-01310.3389/frtra.2024.14486501448650Cord blood T regulatory cells synergize with ruxolitinib to improve GVHD outcomesKe Zeng0Hongbing Ma1Meixian Huang2Mi-Ae Lyu3Tara Sadeghi4Christopher R. Flowers5Simrit Parmar6Department of Lymphoma/Myeloma, The University of Texas at MD Anderson Cancer Center, Houston, TX, United StatesDepartment of Hematology, West China Hospital, Sichuan University, Chengdu, ChinaDepartment of Lymphoma/Myeloma, The University of Texas at MD Anderson Cancer Center, Houston, TX, United StatesDepartment of Lymphoma/Myeloma, The University of Texas at MD Anderson Cancer Center, Houston, TX, United StatesCellenkos Inc., Houston, TX, United StatesDepartment of Lymphoma/Myeloma, The University of Texas at MD Anderson Cancer Center, Houston, TX, United StatesDepartment of Microbial Pathogenesis & Immunology, Texas A&M University, Bryan, TX, United StatesBackgroundAdoptive therapy with umbilical cord blood (UCB) T-regulatory (Treg) cells can prevent graft vs. host disease (GVHD). We hypothesize that UCB Tregs can treat GVHD and synergize with ruxolitinib, Jak2 inhibitor, to improve outcomes.MethodsUCB Treg potency and efficacy was examined using cell suppression assay and xenogeneic GVHD model, respectively. Ruxolitinib was fed continuously in presence or absence of CellTraceViolet tagged UCB Tregs on days +4, +7, +11, +18. Mice were followed for survival, GVHD score, hematology parameters and inflammation.ResultsAddition of ruxolitinib to UCB Tregs exerted synergistic suppressor function in vitro and improved persistence of UCB Tregs in vivo. Lower GVHD score, improved survival, increased hemoglobin level and platelet count, decreased inflammatory cytokines and decrease in CD3+ T cell lung infiltrate was observed in UCB Tregs+ruxolitinib recipients.ConclusionUCB Treg+Ruxolitinib combination improves outcomes in xenogeneic GVHD and should be explored in a clinical setting.https://www.frontiersin.org/articles/10.3389/frtra.2024.1448650/fullGVHDT regulatory cellallogeneiccord bloodruxolitinib |
| spellingShingle | Ke Zeng Hongbing Ma Meixian Huang Mi-Ae Lyu Tara Sadeghi Christopher R. Flowers Simrit Parmar Cord blood T regulatory cells synergize with ruxolitinib to improve GVHD outcomes Frontiers in Transplantation GVHD T regulatory cell allogeneic cord blood ruxolitinib |
| title | Cord blood T regulatory cells synergize with ruxolitinib to improve GVHD outcomes |
| title_full | Cord blood T regulatory cells synergize with ruxolitinib to improve GVHD outcomes |
| title_fullStr | Cord blood T regulatory cells synergize with ruxolitinib to improve GVHD outcomes |
| title_full_unstemmed | Cord blood T regulatory cells synergize with ruxolitinib to improve GVHD outcomes |
| title_short | Cord blood T regulatory cells synergize with ruxolitinib to improve GVHD outcomes |
| title_sort | cord blood t regulatory cells synergize with ruxolitinib to improve gvhd outcomes |
| topic | GVHD T regulatory cell allogeneic cord blood ruxolitinib |
| url | https://www.frontiersin.org/articles/10.3389/frtra.2024.1448650/full |
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