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Allograft rejection

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

Targets

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

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 Withdrawn from the US market.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 Due to reduced demand and use in the US, the manufacturer has withdrawn muromonab-CD3 from the US market.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) [8]. 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 [5]. | 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 [3,7], 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 [6]. | 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

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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. 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]

6. 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]

7. 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]

8. 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]