Top ▲

Allograft rejection

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.

✖
Disease ID:1260
Name:Allograft rejection
Associated with:1 target
1 immuno-relevant target
4 immuno-relevant ligands

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.

✖
Key to terms and symbols
CD80
Comments:  CD80 is a primary target of the approved anti-rejection drug belatacept.
Ligand interactions: 
Ligand Comments
belatacept
Approved drug for the prophylaxis of organ rejection after kidney transplant in EBV-exposed patients.

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.

✖
Key to terms and symbols Click ligand name to view ligand summary Click column headers to sort
Ligand References Clinical and Disease comments
muromonab-CD3
Immuno Disease Comments: Approved to prevent renal, cardiac and hepatic allograft rejection. Withdrawn from the US market.
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. | View clinical data
Bioactivity Comments: We have been unable to find affinity data for this antibody from any open access source. | View biological activity
belatacept
Immuno Disease Comments: Approved drug for the prophylaxis of organ rejection after kidney transplant in EBV-exposed patients.
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) [9]. 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. | View clinical data
Bioactivity Comments: Belatacept binds to human CD86 with an IC50 of 0.102µg/mL and to CD80 with an IC50 of 0.009µg/mL [6]. | View biological activity
sirolimus
Immuno Disease Comments: Approved specifically as prophylaxis of renal transplant rejection.
Clinical Use: Sirolimus is used for prophylaxis of renal transplant rejection [3,8], 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 [7].
Nab-sirolimus (ABI-009; Fyarro®) is an albumin-bound nanoparticle formulation of sirolimus that was developed by Aadi Bioscience as the first treatment for advanced malignant perivascular epithelioid cell neoplasms (PEComa; see NCT02494570) [5,10]. Fyarro® was approved by the FDA in November 2021.
In May 2023 the EMA expanded authorisation to include the treatrment of angiofibroma of tuberous sclerosis. | View clinical data
Bioactivity Comments: In vitro studies have been performed and these show that sirolimus inhibits MERS-CoV infection of Huh7 cells [2,4]. This mechanism could also be applied to SAR-CoV-2 infection. | View biological activity
basiliximab
Immuno Disease Comments: Used in combination with other anti-rejection drugs (cyclosporin A, corticosteroids, azathioprine and mycophenolate mofetil) to prevent renal allograft rejection.
Clinical Use: Prophylaxis of acute organ rejection in adults following cadaveric- or living-donor renal transplantation | View clinical data
Bioactivity Comments: Peptide sequence analysis reveals that patent US6383487 [1] covers the design and uses of basiliximab. However, this patent does not provide affinity data for the interaction between the antibody and its target, IL-2, and we have been unable to find accessible data elsewhere. | View biological activity

References

Show »

1. Amlot PL, Akbar AN, Heinrich G, Cammisuli S. (2002) Methods Of Treatment Using Cd25 Binding Molecules. Patent number: US6383487. Assignee: Novartis Ag, University College London. Priority date: 16/03/1990. Publication date: 07/05/2002.

2. Dyall J, Gross R, Kindrachuk J, Johnson RF, Olinger Jr GG, Hensley LE, Frieman MB, Jahrling PB. (2017) Middle East Respiratory Syndrome and Severe Acute Respiratory Syndrome: Current Therapeutic Options and Potential Targets for Novel Therapies. Drugs, 77 (18): 1935-1966. [PMID:29143192]

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

4. Kindrachuk J, Ork B, Hart BJ, Mazur S, Holbrook MR, Frieman MB, Traynor D, Johnson RF, Dyall J, Kuhn JH et al.. (2015) Antiviral potential of ERK/MAPK and PI3K/AKT/mTOR signaling modulation for Middle East respiratory syndrome coronavirus infection as identified by temporal kinome analysis. Antimicrob Agents Chemother, 59 (2): 1088-99. [PMID:25487801]

5. Kopparthy P, Murphy M. (2021) Rapid and Durable Response With Nab-Sirolimus After Everolimus Failure in a Patient With Perivascular Epithelioid Cell Tumors (PEComas) of the Uterus. Cureus, 13 (5): e14951. DOI: 10.7759/cureus.14951 [PMID:34123648]

6. Latek R, Fleener C, Lamian V, Kulbokas 3rd E, Davis PM, Suchard SJ, Curran M, Vincenti F, Townsend R. (2009) Assessment of belatacept-mediated costimulation blockade through evaluation of CD80/86-receptor saturation. Transplantation, 87 (6): 926-33. [PMID:19300198]

7. 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]

8. 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]

9. 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]

10. Wagner AJ, Ravi V, Riedel RF, Ganjoo K, Van Tine BA, Chugh R, Cranmer L, Gordon EM, Hornick JL, Du H et al.. (2021) nab-Sirolimus for Patients With Malignant Perivascular Epithelioid Cell Tumors. J Clin Oncol, 39 (33): 3660-3670. [PMID:34637337]