A comparative study of human‐and rhesus‐specific antithymocyte globulins in Rhesus macaques

Abstract

Kidney allotransplantation is a life-saving operation with superior mortality and economic outcomes compared with dialysis. 1,2 In the United States, approximately 70% of kidney recipients are treated with depletional induction, typically rabbit antithymocyte globulin (RATG). Multiple clinical studies have shown that RATG reliably decreases the incidence of acute rejection. [3][4][5] As such, depletional induction with RATG is increasingly considered as a therapeutic approach for novel immunosuppressive regimens in preclinical investigation. Nonhuman primates such as rhesus monkeys are commonly used preclinically to test new immunosuppressants.Rabbit antithymocyte globulin is a polyclonal antibody preparation that is developed by immunizing large numbers of rabbits with thymocytes from another species. 6 It works by a variety of mechanisms including direct depletion of lymphocytes and interference

Malnutrition and immune cell subsets in children undergoing kidney transplantation

“…31 This could have two potential effects. First, this may lead to a greater amount of repopulation occurring via peripheral homeostatic proliferation, which is known to skew towards memory phenotypes both generally 32 and in response to polyclonal antibody depletion specifically, 33 which is consistent with our data. Secondly, it may affect the efficacy of calcineurin inhibitors as these drugs have a very narrow therapeutic window and are exceedingly lipophilic.…”

Anti‐thymoglobulin induction improves neonatal porcine xenoislet engraftment and survival

“…31 We argue that rhATG, which is prepared in a parallel fashion to ATG, may serve as an accurate surrogate in the rhesus model. 22 We show that rhATG reliably depletes T cells with the effect persisting throughout the study period.…”

“…We have recently reported on the development of a novel rhesusspecific anti-thymocyte globulin (rhATG), a polyclonal IgG preparation purified from rabbits immunized against thymus recovered from rhesus macaques which serves to emulate the effect of ATG in humans. 22 Although non-depletional induction using basiliximab or daclizumab has been used in early clinical islet transplant studies, 23 most contemporary protocols prefer depletional induction using thymoglobulin, and to a lesser extend alemtuzumab, in combination with a TNFɑ inhibitor. [24][25][26][27][28] A pilot clinical xenotransplantation study conducted in China suggests depletional induction using OKT-3 may be associated with improved neonatal porcine islet (NPI) survival.…”

Clinically available immunosuppression averts rejection but not systemic inflammation after porcine islet xenotransplant in cynomolgus macaques

“…Similar to others, we observed near total depletion of the lymphocytes using rATG in Cohort 5; however, utilization of a species-specific ATG may confer benefits beyond depletion that have been described in the clinical situation. 89 islets. 9 Of note, this regimen, compared with Cohort 1-3 regimens, also promoted the production of immunoregulatory molecules at the transplant site.…”