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. Author manuscript; available in PMC: 2020 Jan 1.

Published in final edited form as: Transplantation. 2019 Jan;103(1):168–176. doi: 10.1097/TP.0000000000002417

Figure 1: — aCD40/Bela/hATG: Two to 3 weeks before combined islet and kidney transplantation (CIKTx), cynomolgus monkey recipients received streptozotocin (STZ: 75 mg/kg) for induction of diabetes. After transplantation, the CIKTx or kidney transplant (KTx)-alone recipients received the same immunosuppressive therapy with anti-CD40 mAb and rapamycin for 4 months. Anti-inflammatory therapies included anti-IL-6R mAb (10 mg/kg) and TNF-alpha receptor fusion protein (Etanercept: 25 mg) up to day 10 (A).³ At four months after transplantation, all recipients were conditioned with total body irradiation (TBI: 1.5 Gy × 2 on days −6 and −5, relative to DBMT), local thymic irradiation (TI: 7 Gy on day −1, relative to DBMT), and horse anti-thymocyte globulin (hATG: 50 mg/kg ×c 3 on days −2, −1 and 0, relative to DBMT). Following donor bone marrow transplantation (DBMT), the recipients were treated with dual costimulatory blockade (CB) with anti-CD40 mAb (20 mg/kg, on post-DBMT days 0, 2, 5, 7, 9, and 12) and belatacept (20 mg/kg, on post-DBMT days 0, 2, 5, and 15). Cyclosporine A (CyA) was administered for 28 days following DBMT, after which no immunosuppression was administered (A).

Bela/hATG: In a previous study, the conditioning regimen consisted of low-dose TBI (1.5 Gy × 2) on days −6 and −5 relative to simultaneous kidney and bone marrow transplantation (SKBMT), TI on day-1, hATG (50 mg/kg × 3 on days −2, −1, and 0) and belatacept (20 mg/kg × 4 on days 0, 2, 5, and 15). A 1-month course of CyA was administered to maintain therapeutic trough levels of 250–350 ng/ml (B).¹

Bela/rATG: In the previous deceased donor study, all recipients initially underwent KTx alone with a conventional triple drug immunosuppressive regimen consisting of tacrolimus, mycophenolate mofetil, and prednisone (B). Four months after KTx alone, the recipients underwent conditioning and DBMT (delayed-DBMT). The conditioning regimen for DBMT is same as the Bela/hATG regimen, except the hATG was replaced with rATG (B).²

Figure 1: — aCD40/Bela/hATG: Two to 3 weeks before combined islet and kidney transplantation (CIKTx), cynomolgus monkey recipients received streptozotocin (STZ: 75 mg/kg) for induction of diabetes. After transplantation, the CIKTx or kidney transplant (KTx)-alone recipients received the same immunosuppressive therapy with anti-CD40 mAb and rapamycin for 4 months. Anti-inflammatory therapies included anti-IL-6R mAb (10 mg/kg) and TNF-alpha receptor fusion protein (Etanercept: 25 mg) up to day 10 (A).³ At four months after transplantation, all recipients were conditioned with total body irradiation (TBI: 1.5 Gy × 2 on days −6 and −5, relative to DBMT), local thymic irradiation (TI: 7 Gy on day −1, relative to DBMT), and horse anti-thymocyte globulin (hATG: 50 mg/kg ×c 3 on days −2, −1 and 0, relative to DBMT). Following donor bone marrow transplantation (DBMT), the recipients were treated with dual costimulatory blockade (CB) with anti-CD40 mAb (20 mg/kg, on post-DBMT days 0, 2, 5, 7, 9, and 12) and belatacept (20 mg/kg, on post-DBMT days 0, 2, 5, and 15). Cyclosporine A (CyA) was administered for 28 days following DBMT, after which no immunosuppression was administered (A).

Bela/hATG: In a previous study, the conditioning regimen consisted of low-dose TBI (1.5 Gy × 2) on days −6 and −5 relative to simultaneous kidney and bone marrow transplantation (SKBMT), TI on day-1, hATG (50 mg/kg × 3 on days −2, −1, and 0) and belatacept (20 mg/kg × 4 on days 0, 2, 5, and 15). A 1-month course of CyA was administered to maintain therapeutic trough levels of 250–350 ng/ml (B).¹

Bela/rATG: In the previous deceased donor study, all recipients initially underwent KTx alone with a conventional triple drug immunosuppressive regimen consisting of tacrolimus, mycophenolate mofetil, and prednisone (B). Four months after KTx alone, the recipients underwent conditioning and DBMT (delayed-DBMT). The conditioning regimen for DBMT is same as the Bela/hATG regimen, except the hATG was replaced with rATG (B).²