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Graft versus host disease

GtoPdb Disease Summaries

This section gives an overview of the disease, and where available shows the following:

  • Synonyms: Shows known synonyms for the disease.
  • Description: Gives a basic description/definition of the disease.
  • Database Link: External links to the same disease at the Disease Ontology, OMIM or Orphanet sites.
  • Immunopharmacology comments: General comments about the target's role in immunopharmacology, provided by GtoImmuPdb curators.
  • Associated with: Counts are displayed for the total targets the disease is associated with in GtoPdb. The counts of targets and ligands of immunological relevance associated to the disease are also shown.

More information can be found in the help pages.

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Disease ID:1220
Name:Graft versus host disease
Associated with:1 target
1 immuno-relevant target
7 immuno-relevant ligands
Synonyms
graft-versus-host disease | GvHD
Description
Rejection of non-self transplanted tissue. GvHD is a possible complication of a bone marrow or stem cell transplant but the term is also used to describe rejection of other types of tissue graft.

Targets

GtoPdb Disease Summaries - Targets

Click on the target name to link to its detailed view page

Where available, information is display on the role of the target in the disease; drugs which target the disease and their therapeutic use and side-effects.

If there is mutation data curated in GtoPdb this is indicated, with a link back to the appropriate section on the target detailed view page

Immuno ligand interactions - If available, a table of immuno-relevant ligands is shown. These ligands have been curated as having an association to the disease and possess interaction data with the target in GtoPdb. The approval status of the ligand is shown, along with curator comments and an indication of whether the target is considered the primary target of the ligand.

More information can be found in the help pages.

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Key to terms and symbols
CD86
Comments:  CD86 is a primary target of the approved anti-rejection drug belatacept.

Ligands

GtoPdb Disease Summaries - Ligands

Click ligand name to view ligand summary page

  • Approved: If the ligand is an approved drug this is indicated, along with approval bodies.
  • Immuno: Immuno icon indicates the ligand is immuno-relevant

Click the arrow in the final column to expand comments

  • Immuno Disease Comments: Curatorial comments specifically added as part of GtoImmuPdb. They give more information on the association between the ligand and disease in the context of immunopharmacology.
  • Clinical Use: General clinical comments relating to the ligand and may not necessarily be specific to the disease in question. With hyperlink to more details on the ligand summary pages.
  • Bioactivty Comments: Curatorial comments specifically about the compounds biological activity - with hyperlink to more details on the ligand summary pages.

More information can be found in the help pages.

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Key to terms and symbols Click ligand name to view ligand summary Click column headers to sort
Ligand References Clinical and Disease comments
alvelestat
Immuno Disease Comments: A Phase 2 clinical candidate for bronchiolitis obliterans syndrome resulting from chronic GVHD.
Clinical Use: A series of Phase 1 and Phase 2 results are reported in clinicaltrials.gov entries | View clinical data
Bioactivity Comments: In contrast with ONO6818, an inhibitor that binds covalently to NE, AZD9668 exhibited a more rapid association and dissociation rate, and its interaction with NE was fully reversible. It also generally showed greater specificity than ONO6818 or for NE over other neutrophil-derived serine proteases, particularly Pr-3 and pancreatic elastase [6]. Approximately 90 analogues are listed in a patent [1] where this is example 94, but only limited SAR data is included. | View biological activity
itacitinib
Immuno Disease Comments: Phase 3 clinical candidate for acute GvHD (see NCT03139604).
Clinical Use: INCB039110 is being assessed in Phase 2 clinical trials as a potential treatment for indications such as rheumatoid arthritis (RA), post essential thrombocythemia myelofibrosis, chronic plaque psoriasis and non-small cell lung cancer (NSCLC). Phase 3 trials in chronic graft-versus-host disease are also underway. Click here to link to ClinicalTrials.gov's complete list of INCB039110 studies. | View clinical data
ibrutinib
Immuno Disease Comments: Approved drug for chronic GvHD.
Clinical Use: Ibrutinib is approved to treat patients with mantle cell lymphoma (MCL), a rare and aggressive type of leukemia, especially patients with MCL who have received at least one prior therapy. In Feb 2014 ibrutinib was granted US FDA approval for treating chronic lymphocytic leukemia (CLL), as with MCL, this is only indicated for patients who have received at least one prior therapy. In February 2015, the US FDA expanded approval to include the treatment of Waldenström's macroglobulinemia (WM), which is a form of type of non-Hodgkin's lymphoma. Approval was granted based on the outcome of clinical trial NCT01614821 which indicated that the drug can offer a substantial improvement over contemporary therapies.
In August 2017, the FDA expanded approval to include treatment of chronic graft versus host disease (cGVHD) after failure of one or more lines of systemic therapy (e.g. first-line corticosteroid therapy). This approval followed results from clinical trial NCT02195869. The recommended dose of ibrutinib for cGVHD is 420 mg, orally once daily. | View clinical data
cyclosporin A
Immuno Disease Comments: Cyclosporin A is approved as an anti-rejection drug.
Clinical Use: Cyclosporine is a powerful immunosupressant. Its inhibitory action on T-lymphocyte activation is used to circumvent graft rejection following autologous organ and tissue transplant. It can also be used to treat severe active, refractory rheumatoid arthritis and severe recalcitrant plaque psoriasis. Across the European Union ophthalmic solutions of cyclosporin are fully approved for the treatment of severe keratitis (corneal inflammation) and severe vernal keratoconjunctivitis (a form of chronic eye allergy that can lead to corneal ulcers and loss of sight; in patients aged 4yrs- adolescent), and it has current orphan designation for 8 indications (click here to link to the EMA's list of orphan designations for cyclosporin).
In August 2018 the FDA approved a 0.09% cyclosporine ophthalmic solution called Cequa® as a topical treatment for keratoconjunctivitis sicca (dry eye). | View clinical data
begelomab
Immuno Disease Comments: Ex Phase 3 clinical candidate for steroid-resistant GvHD- see NCT02411084.
Clinical Use: Begelomab reached Phase clinical trial as a potential therapy for steroid-resistant acute graft versus host disease (GvHD). | View clinical data
Bioactivity Comments: EP2767549 A1 [4] does not provide a precise dissociation constant value for any preferred antibodies. In the table below, we present a value which the author suggests would be the desireable affinity of a preferred antibody. | View biological activity
galectin-1 2
Immuno Disease Comments: Gal-1 reduces host alloreactivity and suppresses the graft versus host immune response in animal GvHD models, leading to increased survival.
belumosudil 3,5
Immuno Disease Comments: FDA approved for this disorder in July 2021.
Clinical Use: Belumosudil (KD025) was evaluated in clinical studies for immunosuppressive, anti-inflammatory and anti-fibrotic efficacy. The FDA approved belumosudil (Rezurock®) in July 2021, as a treatment for chronic graft-versus-host disease that has failed to be controlled by at least two prior lines of systemic therapy. | View clinical data

References

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1. Andersson, Marjana et al.. (2007) 2-Pyridone Derivatives As Neutrophil Elastase Inhibitors And Their Use. Patent number: US20070203129. Assignee: AstraZeneca. Priority date: 15/09/2004. Publication date: 30/08/2007.

2. Baum LG, Blackall DP, Arias-Magallano S, Nanigian D, Uh SY, Browne JM, Hoffmann D, Emmanouilides CE, Territo MC, Baldwin GC. (2003) Amelioration of graft versus host disease by galectin-1. Clin Immunol, 109 (3): 295-307. [PMID:14697744]

3. Cutler C, Lee SJ, Arai S, Rotta M, Zoghi B, Lazaryan A, Ramakrishnan A, DeFilipp Z, Salhotra A, Chai-Ho W et al.. (2021) Belumosudil for chronic graft-versus-host disease after 2 or more prior lines of therapy: the ROCKstar Study. Blood, 138 (22): 2278-2289. [PMID:34265047]

4. Di Naro AF. (2014) Anti-CD26 Antibodies and Uses Thereof. Patent number: EP2767549 A1. Assignee: Adienne S.A.. Priority date: 19/02/2013. Publication date: 20/08/2014.

5. Jagasia M, Lazaryan A, Bachier CR, Salhotra A, Weisdorf DJ, Zoghi B, Essell J, Green L, Schueller O, Patel J et al.. (2021) ROCK2 Inhibition With Belumosudil (KD025) for the Treatment of Chronic Graft-Versus-Host Disease. J Clin Oncol, 39 (17): 1888-1898. DOI: 10.1200/JCO.20.02754 [PMID:33877856]

6. Stevens T, Ekholm K, Gränse M, Lindahl M, Kozma V, Jungar C, Ottosson T, Falk-Håkansson H, Churg A, Wright JL et al.. (2011) AZD9668: pharmacological characterization of a novel oral inhibitor of neutrophil elastase. J Pharmacol Exp Ther, 339 (1): 313-20. [PMID:21791628]