TY - JOUR
T1 - Immune regulatory cell infusion for graft-versus-host disease prevention and therapy
AU - Blazar, Bruce R.
AU - MacDonald, Kelli P.A.
AU - Hill, Geoffrey R.
N1 - Publisher Copyright:
© 2018 by The American Society of Hematology.
PY - 2018/6/14
Y1 - 2018/6/14
N2 - 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.
AB - 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.
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U2 - 10.1182/blood-2017-11-785865
DO - 10.1182/blood-2017-11-785865
M3 - Review article
C2 - 29728401
AN - SCOPUS:85048732843
SN - 0006-4971
VL - 131
SP - 2651
EP - 2660
JO - Blood
JF - Blood
IS - 24
ER -