Zeng Ke, Ma Hongbing, Huang Meixian, Lyu Mi-Ae, Sadeghi Tara, Flowers Christopher R, Parmar Simrit
Department of Lymphoma/Myeloma, The University of Texas at MD Anderson Cancer Center, Houston, TX, United States.
Department of Hematology, West China Hospital, Sichuan University, Chengdu, China.
Front Transplant. 2024 Dec 11;3:1448650. doi: 10.3389/frtra.2024.1448650. eCollection 2024.
Adoptive 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.
UCB 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.
Addition of ruxolitinib to UCB Tregs exerted synergistic suppressor function and improved persistence of UCB Tregs . 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.
UCB Treg+Ruxolitinib combination improves outcomes in xenogeneic GVHD and should be explored in a clinical setting.
采用脐带血（UCB）调节性T细胞（Treg）进行过继性治疗可预防移植物抗宿主病（GVHD）。我们假设UCB Tregs可以治疗GVHD，并与JAK2抑制剂鲁索替尼协同作用以改善治疗效果。
分别使用细胞抑制试验和异种GVHD模型检测UCB Treg的效力和疗效。在第4、7、11、18天，在有或无CellTraceViolet标记的UCB Tregs存在的情况下持续给予鲁索替尼。对小鼠进行生存、GVHD评分、血液学参数和炎症监测。
将鲁索替尼添加到UCB Tregs中可发挥协同抑制功能，并改善UCB Tregs的持久性。在接受UCB Tregs+鲁索替尼治疗的小鼠中，观察到GVHD评分降低、生存率提高、血红蛋白水平和血小板计数增加、炎性细胞因子减少以及CD3 T细胞肺浸润减少。
UCB Treg+鲁索替尼联合治疗可改善异种GVHD的治疗效果，应在临床环境中进行探索。
