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 |
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| Institution: | 1. Pediatric Hematology-Oncology Fellow, Memorial Sloan Kettering Cancer Center, and Department of Pediatrics, Weill Cornell Medical College of Cornell University, New York, New York, USA;2. Center for Cancer and Immunology Research, CETI, Children''s National Hospital, Washington, District of Columbia, USA;3. Division of Hematology, Oncology, Stem Cell Transplantation and Regenerative Medicine, Department of Pediatrics, Stanford University, Stanford, California, USA;4. Department of Bone Marrow Transplantation and Cellular Therapy, St Jude Children''s Research Hospital, Memphis, Tennessee, USA;5. Pediatric Blood and Marrow Transplantation Division and Pele Pequeno Principe Research Institute, Hospital Pequeno Principe, Curitiba, Brazil;6. Universite de Montreal and Maisonneuve Rosemont Hospital, Montreal, Quebec, Canada;7. Bone Marrow Failure and MDS Program, John Hopkins Medicine Baltimore, Maryland, USA;8. CRISPR Therapeutics Cambridge, Massachusetts, USA;9. Stem Cell Transplantation and Cellular Therapies, Memorial Sloan Kettering Cancer Center, New York, New York, USA;10. Department of Pediatrics, Division of Stem Cell Transplantation and Regenerative Medicine, Redwood City, California, USA;11. Department of Haematology, Fiona Stanley Hospital, Perth, Western Australia, Australia;12. IRCCS Ospedale San Raffaele, Segrate, Milan, Italy;13. Center for Cellular Immunotherapies, University of Pennsylvania, Philadelphia, Pennsylvania, USA;14. Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, UK;15. Stem Cell Transplantation and Cellular Therapies, Memorial Sloan Kettering Cancer Center, and Department of Pediatrics, Weill Cornell Medical College of Cornell University, New York, New York, USA;16. Dana-Farber/Boston Children''s Cancer and Blood Disorders Center, Boston, Massachusetts USA |
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| Abstract: | Background aimsAllogeneic 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.MethodsWe 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.ResultsAlthough 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.ConclusionsThere 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. |
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