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ORIGINAL RESEARCH article

Front. Transplant.
Sec. Cell and Stem Cell Transplantation
Volume 3 - 2024 | doi: 10.3389/frtra.2024.1448650
This article is part of the Research Topic Immunology of Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) View all 9 articles

Cord Blood T Regulatory Cells Synergize with Ruxolitinib to Improve GVHD Outcomes

Provisionally accepted
KE ZENG KE ZENG 1Hongbing Ma Hongbing Ma 1Meixian Huang Meixian Huang 1Mi-Ae Lyu Mi-Ae Lyu 1Tara Sadeghi Tara Sadeghi 2Christopher R Flowers Christopher R Flowers 1Simrit Parmar Simrit Parmar 1*
  • 1 University of Texas MD Anderson Cancer Center, Houston, United States
  • 2 Cellenkos Inc., Houston, Texas, United States

The final, formatted version of the article will be published soon.

    Background: 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. Methods: 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. Results: Addition 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. Conclusion: UCB Treg + Ruxolitinib combination improves outcomes in xenogeneic GVHD and should be explored in a clinical setting.

    Keywords: GvHD, T regulatory cell, Allogeneic, cord blood, Ruxolitinib

    Received: 13 Jun 2024; Accepted: 18 Nov 2024.

    Copyright: © 2024 ZENG, Ma, Huang, Lyu, Sadeghi, Flowers and Parmar. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Simrit Parmar, University of Texas MD Anderson Cancer Center, Houston, United States

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