Abstract
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.
Key Words
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Article info
Publication history
Published online: March 18, 2023
Accepted:
February 15,
2023
Received:
November 4,
2022
Publication stage
In Press Corrected ProofIdentification
Copyright
Published by Elsevier Inc. on behalf of International Society for Cell & Gene Therapy.
