Transplant Immunosuppression Posters

Monday July 02, 2018 from 16:30 to 17:30

Room: Hall 10 - Exhibition

P.257 Comparative study of human and cynomolgus t-cell depletion with rabbit anti-thymocyte globulin (rATG) treatment - for dose adjustment in a non-human primate transplantation model

Sungjoo Kim, Korea

Prof.
Surgery
Sungkyunkwan university

Abstract

Comparative Study of Human and Cynomolgus T-cell Depletion with Rabbit Anti-Thymocyte Globulin (rATG) Treatment - For Dose Adjustment in a Non-Human Primate Transplantation Model

Kyo Won Lee1, Min Jung Kim2, Jae Berm Park1, Sung Joo Kim1, Ji Soo Lee1, Young Bin Kwon1.

1Department of Surgery, Samsung Medical Center, Seoul, Korea; 2Department of Surgery, Seoul Medical Center, Seoul, Korea

Rabbit-antithymocyte globulin (rATG) is commonly used in solid organ transplantation to prevent and treat allograft rejection. Although rATG is also commonly used in non-human primates, the optimal dose has not been reported. In this study, we evaluated which cumulative dose of rATG was most appropriate for transplantation in a non-human primate (NHP). Cynomolgus monkeys were treated with 5 mg/kg of rATG (Thymoglobulin®, Genzyme Ltd., UK) intravenously twice on day 0 and 2 (a total of 10 mg/kg, n = 2) or 4 times on day 0, 1, 2 and 3 (a total of 20 mg/kg, n = 6). And, we performed an allo-kidney transplantation (KT) in cynomolgus monkeys (n = 4) with a cumulatively 20 mg/kg of rATG induction. Also their subpopulation of T cells like naïve, central memory and effector memory T cells were compared in the kinetics of human KT patients (n = 7). The kinetics of lymphocytes decreased rapidly at day 1 and then was maintained for 2 weeks in the 20 mg/kg rATG group, while maintenance was not observed in the 10 mg/kg rATG group. During the early period of rATG treatment in NHP KT model, their T cell subpopulation in the 20 mg/kg group showed a similar pattern of change to kidney transplant patients treated with rATG (1.5 mg/kg, 3 days). However, the pattern of B cells was different from those of human KT patients. These data indicate that the lymphocyte-depletion induced by rATG was influenced by the cumulative dose, and that anrATG dose of 20 mg/kg is suitable for induction therapy in renal transplantation in cynomolgus monkeys when compared to human KT.



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