Abstract

Graft-versus-host disease (GVHD) is a serious and deadly complication of patients, who undergo hematopoietic stem cell transplantation (HSCT). Despite prophylactic treatment with immunosuppressive agents, 20–80% of recipients develop acute GVHD after HSCT. And the incidence rates of chronic GVHD range from 6 to 80%. Standard therapeutic strategies are still lacking, although considerable advances have been gained in knowing of the predisposing factors, pathology, and diagnosis of GVHD. Targeting immune cells, such as regulatory T cells, as well as tolerogenic dendritic cells or mesenchymal stromal cells (MSCs) display considerable benefit in the relief of GVHD through the deletion of alloactivated T cells. Monoclonal antibodies targeting cytokines or signaling molecules have been demonstrated to be beneficial for the prevention of GVHD. However, these remain to be verified in clinical therapy. It is also important and necessary to consider adopting individualized treatment based on GVHD subtypes, pathological mechanisms involved and stages. In the future, it is hoped that the identification of novel therapeutic targets and systematic research strategies may yield novel safe and effective approaches in clinic to improve outcomes of GVHD further. In this article, we reviewed the current advances in targeted immunotherapy for the prevention of GVHD.

Highlights

  • Hematopoietic stem cell transplantation (HSCT) is used to treat hematologic malignancies

  • These findings demonstrate the immunosuppressive potential of Tregs in suppressing Graft-versus-host disease (GVHD) without loss of the benefits of graft-versus-leukemia (GVL) activity

  • The overall survival rate at 1 and 2 years was 50.0 and 38.6%, respectively, and the median survival time was 1.1 years from the first mesenchymal stromal cells (MSCs) administration [39]. These findings show that MSC can be safely administered on top of conventional immunosuppression for SR-GVHD treatment

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Summary

INTRODUCTION

Hematopoietic stem cell transplantation (HSCT) is used to treat hematologic malignancies. 20–80% of recipients would develop aGVHD after allogeneic hematopoietic cell transplantation. Despite considerable advances in knowing of the predisposing factors, pathophysiology, and diagnosis of aGVHD and cGVHD, a standard therapeutic strategy is still lacking [6,7,8]. Criteria and indications for secondary systemic therapy of aGVHD have not been systematically defined. Secondary systemic therapy may be indicated earlier in patients who cannot tolerate high-dose glucocorticoid treatment. Agents for second-line treatment of aGVHD include immunosuppressive agents (mycophenolate mofetil, pentostatin, cyclophosphamide) and monoclonal antibodies (mAbs), and so on. Apart from systemic corticosteroids, the therapies targeting immune cells and immune molecular have been applied currently to inhibit GVHD [10,11,12,13,14,15]. We reviewed current advances in immunotherapy for GVHD

IMMUNE CELLS FOR THE TREATMENT OF GVHD
Therapeutic Potential of Tregs for GVHD
Immune cells mAbs to cytokines
Treatment of GVHD With TDCs
Mesenchymal Stromal Cells for the Treatment of GVHDs
Nanoencapsulation of Allogeneic T Cells Mitigates GVHD
TARGETING CYTOKINES FOR THE TREATMENT OF GVHD
TARGETING CD MOLECULES FOR THE TREATMENT OF GVHD
Cells or agents
Signaling molecules
Attenuated the severity and fibrosis of cGVHD
TARGETING SIGNALING MOLECULES FOR THE TREATMENT OF GVHD
Notch Inhibitor for the Treatment of GVHD
Syk Inhibitor
Findings
CONCLUSION
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