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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 Withdrawn from the US market.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 Due to reduced demand and use in the US, the manufacturer has withdrawn muromonab-CD3 from the US market.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) [6]. 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 [3]. | 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 [2,5], 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 [4]. | View clinical data
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. Kelly PA, Gruber SA, Behbod F, Kahan BD. (1997) Sirolimus, a new, potent immunosuppressive agent. Pharmacotherapy, 17 (6): 1148-56. [PMID:9399599]

3. 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]

4. 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]

5. 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]

6. 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]