Cord blood T regulatory cells synergize with ruxolitinib to improve GVHD outcomes

Ke Zeng; Hongbing Ma; Meixian Huang; Mi-Ae Lyu; Tara Sadeghi; Christopher R Flowers; Simrit Parmar

doi:10.3389/frtra.2024.1448650

Cord blood T regulatory cells synergize with ruxolitinib to improve GVHD outcomes

Front Transplant. 2024 Dec 11:3:1448650. doi: 10.3389/frtra.2024.1448650. eCollection 2024.

Authors

Ke Zeng¹, Hongbing Ma², Meixian Huang¹, Mi-Ae Lyu¹, Tara Sadeghi³, Christopher R Flowers¹, Simrit Parmar⁴

Affiliations

¹ Department of Lymphoma/Myeloma, The University of Texas at MD Anderson Cancer Center, Houston, TX, United States.
² Department of Hematology, West China Hospital, Sichuan University, Chengdu, China.
³ Cellenkos Inc., Houston, TX, United States.
⁴ Department of Microbial Pathogenesis & Immunology, Texas A&M University, Bryan, TX, United States.

Abstract

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.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This study was conducted by using funding provided under sponsored research agreement with Cellenkos Inc. Cellenkos Grant #54964. The authors declare that this study received funding from Cellenkos. The funder was not involved in the study design, collection, analysis, interpretation of data, the writing of this article or the decision to submit it for publication.