Immune regulatory cell infusion for graft-versus-host disease prevention and therapy

Bruce R. Blazar, Kelli P.A. MacDonald, Geoffrey R. Hill

Research output: Contribution to journalReview articlepeer-review

82 Scopus citations

Abstract

Current approaches to prevent and treat graft-versushost disease (GVHD) after stem cell transplantation rely principally on pharmacological immune suppression. Such approaches are limited by drug toxicity, nonspecific immune suppression, and a requirement for long-term therapy. Our increased understanding of the regulatory cells and molecular pathways involved in limiting pathogenic immune responses opens the opportunity for the use of these cell subsets to prevent and/or GVHD. The theoretical advantages of this approach is permanency of effect, potential for facilitating tissue repair, and induction of tolerance that obviates a need for ongoing drug therapy. To date, a number of potential cell subsets have been identified, including FoxP3+ regulatory T (Treg) and FoxP3negIL-10+ (FoxP3-negative) regulatory T (Tr1), natural killer (NK) and natural killer T (NKT) cells, innate lymphoid cells, and various myeloid suppressor populations of hematopoietic (eg, myeloid derived suppressor cells) and stromal origin (eg, mesenchymal stem cells). Despite initial technical challenges relating to large-scale selection and expansion, these regulatory lineages are now undergoing early phase clinical testing. To date, Treg therapies have shown promising results in preventing clinical GVHD when infused early after transplant. Results from ongoing studies over the next 5 yearswill delineate themost appropriate cell lineage, source (donor, host, third party), timing, and potential exogenous cytokine support needed to achieve the goal of clinical transplant tolerance.

Original languageEnglish (US)
Pages (from-to)2651-2660
Number of pages10
JournalBlood
Volume131
Issue number24
DOIs
StatePublished - Jun 14 2018

Bibliographical note

Funding Information:
This work was supported by the Australian National Health and Medical Research Council grant APP1031728 (K.P.A.M.), the National Institutes of Health (NIH) National Institute of Allergy and Infectious Diseases grant R37 AI34495, National Heart, Lung, NIH Blood Institute grants R01 HL56067 and HL11879, and NIH National Cancer Institute grants P01 CA142106 and P01 CA065493. G.R.H. is an NH&MRC Senior Principal Research Fellow.

Publisher Copyright:
© 2018 by The American Society of Hematology.

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