International Society for Cell & Gene Therapy Stem Cell Engineering Committee: Cellular therapies for the treatment of graft-versus-host-disease after hematopoietic stem cell transplant.

Background Aims: Allogeneic hematopoietic stem cell transplant is a curative approach for many malignant and non-malignant hematologic conditions. Despite advances in its prevention and treatment, the morbidity and mortality related to graft-versus-host disease (GVHD) remains. The mechanisms by which currently used pharmacologic agents impair the activation and proliferation of potentially alloreactive T cells reveal pathways essential for the detrimental activities of these cell populations. Importantly, these same pathways can be important in mediating the graft-versus-leukemia effect in recipients transplanted for malignant disease. This knowledge informs potential roles for cellular therapies such as mesenchymal stromal cells and regulatory T cells in preventing or treating GVHD. This article reviews the current state of adoptive cellular therapies focused on GVHD treatment.
Methods: We conducted a search for scientific literature in PubMed® and ongoing clinical trials in clinicaltrial.gov with the keywords "Graft-versus-Host Disease (GVHD)," "Cellular Therapies," "Regulatory T cells (Tregs)," "Mesenchymal Stromal (Stem) Cells (MSCs)," "Natural Killer (NK) Cells," "Myeloid-derived suppressor cells (MDSCs)," and "Regulatory B-Cells (B-regs)." All the published and available clinical studies were included.
Results: Although most of the existing clinical data focus on cellular therapies for GVHD prevention, there are observational and interventional clinical studies that explore the potential for cellular therapies to be safe modalities for GVHD treatment while maintaining the graft-versus-leukemia effect in the context of malignant diseases. However, there are multiple challenges that limit the broader use of these approaches in the clinical scenario.
Conclusions: There are many ongoing clinical trials to date with the promise to expand our actual knowledge on the role of cellular therapies for GVHD treatment in an attempt to improve GVHD-related outcomes in the near future.
Competing Interests: Declaration of Competing Interest JJB: Consulting: Avrobio, BlueRock, Race Oncology, Advanced Clinical, Omeros, Sanofi, Medexus, Equillium, Sobi. AA: served on the safety monitoring committee for Sangamo Therapeutics and has no financial interest in the development of gene therapies. SP: Receives support for the conduct of clinical trials through MSK from AlloVir, Atara, and Jasper. Inventor of IP related to development of third-party viral-specific T cells program with all rights assigned to MSK. CB: Consulting: Zodiac, Amgen, Novartis. SC: ExCellThera: royalties, consulting, shares. DP: Novartis – honoraria, Gilead – honoraria, BMS-Celgene – honoraria, Jazz – honoraria, All honoraria were paid to the author's institution (Fiona Stanley Hospital), not the author. AS: Consultant: Spotlight Therapeutics (2020), Medexus Inc. (2021), Vertex Pharmaceuticals (2021). Research Funding: CRISPR Therapeutics (2021-2022). Honoraria: Vindico Medical Education (2020). Research Collaboration: Magenta Therapeutics (2021-Present). Clinical Trial site-PI: CRISPR Therapeutics (2018-Present), Vertex Pharmaceuticals (2018-Present), Novartis (2019-Present), Magenta Therapeutics (2021-Present). MP-D: Equity: GraphiteBio.
(Published by Elsevier Inc.)