Immune Regulatory Cell Biology and Clinical Applications to Prevent or Treat Acute Graft-Versus-Host Disease

Bruce R. Blazar

doi:10.1016/j.eng.2018.11.016

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Engineering ›› 2019, Vol. 5 ›› Issue (1) : 98-105. DOI: 10.1016/j.eng.2018.11.016

Research

Research Immunology—Review

Immune Regulatory Cell Biology and Clinical Applications to Prevent or Treat Acute Graft-Versus-Host Disease

Bruce R. Blazar

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Abstract

The most common approaches to prevent and treat graft-versus-host disease (GVHD) are intended to deplete or suppress the T cells capable of mediating or supporting alloresponses; however, this renders the recipients functionally T cell deficient and hence highly susceptible to infections and tumor recurrence. Depletion is often accomplished through the use of broadly reactive antibodies, while functional impairment is typically achieved by pharmacological agents that require long-term administration (usually six months or more), have significant side effects, and may not result in tolerance (i.e., non-responsiveness) of donor T cells to conditioning regimen-resistant host alloantigen-bearing cells. As our knowledge of immune system homeostasis has increased, cell populations with immune regulatory function have been identified and characterized. Although such cell populations are typically present in low frequencies, methods to isolate and expand these cells have permitted their supplementation to the donor graft or infusion late post-transplant in order to stifle GVHD. This review discusses the biology and preclinical proof of concept of GVHD models, along with GVHD outcomes that focus exclusively on immune regulatory cell therapies that have progressed to clinical testing.

Keywords

Graft-versus-host disease (GVHD) / Immune regulatory cells / Cell therapy

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Bruce R. Blazar. Immune Regulatory Cell Biology and Clinical Applications to Prevent or Treat Acute Graft-Versus-Host Disease. Engineering, 2019, 5(1): 98‒105 https://doi.org/10.1016/j.eng.2018.11.016

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Acknowledgements

This work was supported by grants from the National Institute of Allergy and Infectious Diseases, National Institutes of Health (R37 AI34495), National Heart, Lung, and Blood Institute, National Institutes of Health (R01 HL56067 and R01 HL11879), and National Cancer Institute, National Institutes of Health (P01 CA142106 and P01 CA065493).

The author thanks Drs. Geoff Hill and Kelli MacDonald for their collaboration in assembling literature related to this topic area, to colleagues and laboratory members who have moved the cell therapy field forward, and to patients and families for their participation in clinical trials.