Graft versus host disease

Disease ID:1220
Name:Graft versus host disease
Associated with:2 targets
2 immuno-relevant targets
11 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

CD80
Comments:  CD80 is a primary target of the approved anti-rejection drug belatacept.
Ligand interactions
Ligand Name Disease Association Comments Approved Primary Target Immuno
belatacept
Approved for prophylaxis of organ rejection after kidney transplant.
 [  (Drugs.com) ]
CD86
Comments:  CD86 is a primary target of the approved anti-rejection drug belatacept.
Ligand interactions
Ligand Name Disease Association Comments Approved Primary Target Immuno
belatacept
Approved for prophylaxis of organ rejection after kidney transplant.
 [  (Drugs.com) ]

Ligands

Ligand Approved Immuno References Clinical comments
alvelestat
Clinical Use: A series of Phase I and Phase II results are reported in clinicaltrials.gov entries
Immuno Disease Comments: A Phase 2 clinical candidate for bronchiolitis obliterans syndrome resulting from chronic GVHD.
itacitinib
Clinical Use: INCB039110 is being assessed in Phase II clinical trial 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).
Immuno Disease Comments: Phase 3 clinical candidate for acute GvHD (see NCT03139604).
ibrutinib  [  (Drugs.com) ]
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.
Immuno Disease Comments: Approved drug for chronic GvHD.
begelomab
Clinical Use: Begelomab reached Phase clinical trial as a potential therapy for steroid-resistant acute graft versus host disease (GvHD).
Immuno Disease Comments: Ex Phase 3 clinical candidate for steroid-resistant GvHD- see NCT02411084.
galectin-1 1
Immuno Disease Comments: Gal-1 reduces host alloreactivity and suppresses the graft versus host immune response in animal GvHD models, leading to increased survival.
cyclosporin A  [  (Drugs.com) ]
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. Across the European Union cyclosporin can be used to treat severe keratitis in adults, and has current orphan designation for 8 indications (click here to link to the EMA's list of orphan designations for cyclosporin).
In July 2017, the EMA recommended granting marketing authorisation in the European Union for Verkazia, an ocular formulation containing cyclosporin for the treatment of children (4yrs- adolescent) with the orphan disease severe vernal keratoconjunctivitis (VKC- a form of chronic eye allergy that can lead to corneal ulcers and loss of sight). Cyclosporin in this form had previously received EMA orphan designation for VKC in 2006.
Immuno Disease Comments: Cyclosporin A is approved as an anti-rejection drug.
sirolimus  [  (Drugs.com) ]
Clinical Use: Sirolimus is used for prophylaxis of renal transplant rejection [2,4], and may be used in combination with . In June 2015 the US FDA approved sirolimus for the treatment of lymphangioleiomyomatosis, a rare proliferative but benign lung disease [3].
Immuno Disease Comments: Approved specifically as prophylaxis of renal transplant rejection.
basiliximab  [  (Drugs.com) ]
Clinical Use: Prophylaxis of acute organ rejection in adults following cadaveric- or living-donor renal transplantation
Immuno Disease Comments: Used in combination with other anti-rejection drugs (cyclosporin A, corticosteroids, azathioprine and mycophenolate mofetil) to prevent renal allograft rejection.
muromonab-CD3  [  (Drugs.com) ]
Clinical Use: Used to prevent renal, cardiac and hepatic allograft rejection. Due to reduced demand and use in the US, the manufacturer has withdrawn muromonab-CD3 from the US market.
Immuno Disease Comments: Approved to prevent renal, cardiac and hepatic allograft rejection. Withdrawn from the US market.
belatacept  [  (Drugs.com) ]
Clinical Use: Approved for prophylaxis of organ rejection after kidney transplant.
The first analysis of long-term outcomes (7 years post-transplant) for belatacept-induced immunosuppression compared to cyclosporine treatment are reported by Vincenti et al. (2016) [5]. These results, from clinical trial NCT00256750, show a clear and significant benefit from treating with belatacept rather than cyclosporine. The authors suggest that the improvement is likely due to the alternative mechanism of action of belatacept (blocks T-cell costimulation) and its non-nephrotoxic nature, in comparison to cyclosporine which is often the cause of failure of transplanted kidneys over time.
Immuno Disease Comments: Approved for prophylaxis of organ rejection after kidney transplant.
KD025
Clinical Use: KD025 is in Phase 2 clinical trials evaluating its anti-inflammatory and anti-fibrotic activity.
Immuno Disease Comments: Phase 2 clinical candidate for chronic graft vs. host disease (NCT02841995).

References

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1. 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]

2. Kelly PA, Gruber SA, Behbod F, Kahan BD. (1997) Sirolimus, a new, potent immunosuppressive agent. Pharmacotherapy, 17 (6): 1148-56. [PMID:9399599]

3. McCormack FX, Inoue Y, Moss J, Singer LG, Strange C, Nakata K, Barker AF, Chapman JT, Brantly ML, Stocks JM et al.. (2011) Efficacy and safety of sirolimus in lymphangioleiomyomatosis. N. Engl. J. Med., 364 (17): 1595-606. [PMID:21410393]

4. Vasquez EM. (2000) Sirolimus: a new agent for prevention of renal allograft rejection. Am J Health Syst Pharm, 57 (5): 437-48; quiz 449-51. [PMID:10711524]

5. Vincenti F, Rostaing L, Grinyo J, Rice K, Steinberg S, Gaite L, Moal MC, Mondragon-Ramirez GA, Kothari J, Polinsky MS et al.. (2016) Belatacept and Long-Term Outcomes in Kidney Transplantation. N. Engl. J. Med., 374 (4): 333-43. [PMID:26816011]