Immunosuppression With CD40 Costimulatory Blockade Plus Rapamycin for Simultaneous Islet-Kidney Transplantation in Nonhuman Primates.
Am J Transplant
; 17(3): 646-656, 2017 03.
Article
en En
| MEDLINE
| ID: mdl-27501203
ABSTRACT
The lack of a reliable immunosuppressive regimen that effectively suppresses both renal and islet allograft rejection without islet toxicity hampers a wider clinical application of simultaneous islet-kidney transplantation (SIK). Seven MHC-mismatched SIKs were performed in diabetic cynomolgus monkeys. Two recipients received rabbit antithymocyte globulin (ATG) induction followed by daily tacrolimus and rapamycin (ATG/Tac/Rapa), and five recipients were treated with anti-CD40 monoclonal antibody (mAb) and rapamycin (aCD40/Rapa). Anti-inflammatory therapy, including anti-interleukin-6 receptor mAb and anti-tumor necrosis factor-α mAb, was given in both groups. The ATG/Tac/Rapa recipients failed to achieve long-term islet allograft survival (19 and 26 days) due to poor islet engraftment and cytomegalovirus pneumonia. In contrast, the aCD40/Rapa regimen provided long-term islet and kidney allograft survival (90, 94, >120, >120, and >120 days), with only one recipient developing evidence of allograft rejection. The aCD40/Rapa regimen was also tested in four kidney-alone transplant recipients. All four recipients achieved long-term renal allograft survival (100% at day 120), which was superior to renal allograft survival (62.9% at day 120) with triple immunosuppressive regimen (tacrolimus, mycophenolate mofetil, and steroids). The combination of anti-CD40 mAb and rapamycin is an effective and nontoxic immunosuppressive regimen that uses only clinically available agents for kidney and islet recipients.
Palabras clave
animal models: nonhuman primate; costimulation; fusion proteins and monoclonal antibodies; immunosuppressant; immunosuppression/immune modulation; islet transplantation; islets of Langerhans; kidney transplantation/nephrology; mechanistic target of rapamycin: sirolimus; translational research/science
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Trasplante de Islotes Pancreáticos
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Trasplante de Riñón
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Sirolimus
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Diabetes Mellitus
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Supervivencia de Injerto
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Suero Antilinfocítico
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Am J Transplant
Asunto de la revista:
TRANSPLANTE
Año:
2017
Tipo del documento:
Article
País de afiliación:
Marruecos