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

In this study, we evaluated which cumulative dose of rATG was most appropriate for transplantation in NHPs. Cynomolgus monkeys were treated with intravenous 5 mg/kg rATG (Thymoglobulin®, Genzyme Ltd., UK) twice, on days 0 and 2 (a total of 10 mg/kg, n=2), or 4 times, on days 0, 1, 2, and 3 (a total of 20 mg/kg, n=6). In addition, we performed allo-KT in cynomolgus monkeys (n=4) with a cumulative 20 mg/kg dose of rATG with optimized dosing for induction therapy. We further compared immune cells, including naïve, central memory, and effector memory T cells, in reconstituted distributions in human KT patients (n=22). The kinetics of lymphocytes showed a rapid decrease at day 1 that was maintained for 2 weeks in the 20 mg/kg rATG group, while lymphocyte depletion was not maintained for more than 1 week in the 10 mg/kg rATG group. During the early period of rATG treatment in the NHP-KT model, the frequency of total T cells in the 20 mg/kg group showed a pattern of depletion similar with that of KT patients treated with rATG (1.5 mg/kg, 3 days). However, the pattern of reconstituted T cell subpopulations was different, as the number of effector memory cells rebounded in the NHP-KT model. These data indicate that lymphocyte-depletion induced by rATG was influenced by cumulative dose, and that an rATG dose of 20 mg/kg is suitable for induction therapy in renal transplantation in cynomolgus monkeys compared to human KT. PMID: 31737194 [PubMed]
Source: American Journal of Translational Research - Category: Research Tags: Am J Transl Res Source Type: research