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Review
. 2022 Nov 17:13:1045168.
doi: 10.3389/fimmu.2022.1045168. eCollection 2022.

Cell-based therapy in prophylaxis and treatment of chronic graft-versus-host disease

Matteo Doglio  1 , Rachel E Crossland  2 , Ana C Alho  3   4 , Olaf Penack  5 , Anne M Dickinson  2   6 , Georg Stary  7   8   9 , João F Lacerda  3   4 , Günther Eissner  10 , Marit Inngjerdingen  11
Affiliations
Review

Cell-based therapy in prophylaxis and treatment of chronic graft-versus-host disease

Matteo Doglio et al. Front Immunol. .

Abstract

Hematopoietic allogeneic stem cell transplantation (allo-SCT) is a curative option for patients with hematological malignancies. However, due to disparities in major and minor histocompatibility antigens between donor and recipient, severe inflammatory complications can occur, among which chronic graft-versus-host disease (cGVHD) can be life-threatening. A classical therapeutic approach to the prevention and treatment of cGVHD has been broad immunosuppression, but more recently adjuvant immunotherapies have been tested. This review summarizes and discusses immunomodulatory approaches with T cells, including chimeric antigen receptor (CAR) and regulatory T cells, with natural killer (NK) cells and innate lymphoid cells (ILCs), and finally with mesenchymal stromal cells (MSC) and extracellular vesicles thereof. Clinical studies and pre-clinical research results are presented likewise.

Keywords: CAR; ILCs; MSCs; NK cells; Tregs; chronic GVHD; extracellular vesicles.

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Conflict of interest statement

AD was employed by Alcyomics Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Cellular therapy for chronic GVHD. The figure illustrates cell types that are currently exploited or that can be exploited for chronic GVHD, and that are discussed in this review.
Figure 2
Figure 2
Exploiting CAR-T cell therapy for chronic GVHD. The engineering of CAR constructs (illustrated in the circle) in conventional T cells or T regulatory cells may be exploited in therapy for chronic GVHD.
Figure 3
Figure 3
Origin of mesenchymal stromal cell extracellular vesicles and putative role for GVHD. Mesenchymal stromal cells (MSC) may be derived from a variety of sources, including bone marrow, adipose tissue, muscle, neonatal tissues, dental pulp and skin. The MSC release extracellular vesicles (EV) by inward budding of the plasma membrane and formation of intracellular multivesicular bodies (MVB), followed by exocytosis. MSC-derived EVs are enriched in various proteins with multiple functions, such as biogenesis-related proteins (e.g., TSG101, ALIX), common surface markers (e.g., CD9, CD81, CD29, CD44 and CD90), membrane transporter and fusion proteins (e.g., Rab GTPases and annexins), integrins, heat shock proteins (e.g., HSP60, HSP70 and HSP90) and MHC class I and II proteins, DNA, RNA and noncoding RNA (ncRNA), including miRNA, lncRNA, and circRNA. The MSC-EVs may modulate acute or chronic GVHD by acting on diverse immune cells.
See this image and copyright information in PMC

References

    1. Penack O, Marchetti M, Ruutu T, Aljurf M, Bacigalupo A, Bonifazi F, et al. . Prophylaxis and management of graft versus host disease after stem-cell transplantation for haematological malignancies: updated consensus recommendations of the European society for blood and marrow transplantation. Lancet Haematology (2020) 7:e157–67. doi: 10.1016/S2352-3026(19)30256-X - DOI - PubMed
    1. Velickovic VM, McIlwaine E, Zhang R, Spelman T. Adverse events in second-and third-line treatments for acute and chronic graft-versus-host disease: Systematic review. Ther Adv Hematol (2020) 11:2040620720977039. doi: 10.1177/2040620720977039 - DOI - PMC - PubMed
    1. Voermans C, Hazenberg MD. Cellular therapies for graft-versus-host disease: a tale of tissue repair and tolerance. Blood (2020) 136:410–7. doi: 10.1182/blood.2019000951 - DOI - PubMed
    1. Edinger M, Hoffmann P, Ermann J, Drago K, Fathman CG, Strober S, et al. . CD4+ CD25+ regulatory T cells preserve graft-versus-tumor activity while inhibiting graft-versus-host disease after bone marrow transplantation. Nat Med (2003) 9:1144–50. doi: 10.1038/nm915 - DOI - PubMed
    1. Di Ianni M, Falzetti F, Carotti A, Terenzi A, Castellino F, Bonifacio E, et al. . Tregs prevent GVHD and promote immune reconstitution in HLA-haploidentical transplantation. Blood J Am Soc Hematol (2011) 117:3921–8. doi: 10.1182/blood-2010-10-311894 - DOI - PubMed

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