Session Time: 2:30pm-4:00pm
Presentation Time: 2:54pm-3:06pm
Purpose: Spontaneous liver tolerance occurs in highly selected patients with stable liver function. There is an unmet need for a safe and reliable regimen allowing rapid immunosuppression (IS) withdrawal. We investigated if tolerance to liver allografts can be achieved using a mixed chimerism (MC) approach.
Methods: 9 combined liver and bone marrow transplantations (CLBMT) were performed in cynomolgus macaques, using 3 different non-myeloablative conditioning regimens. All animals received total body irradiation, thymic irradiation, and ATGAM prior to CLBMT. Rituximab, anti-CD40, and LoCD2b monoclonal antibodies were given according to Table 1. All IS was withdrawn by day 50.
Results: All recipients developed MC. Group A showed severe rejection with T effector memory (Tmem) expansion. Improved pre-transplant Tmem deletion using LoCD2b in group B resulted in prolonged MC and graft acceptance. B(2), however, developed GVHD. Addition of post-transplant depletion of donor and host Tmem with LoCD2b permitted prolonged MC, no GVHD, and extended graft survival.
|Protocol (animal#)||MHC mismatch||Induction|
Conclusions: This is the first proof of concept study demonstrating tolerance induction via CLBMT in nonhuman primates.
CITATION INFORMATION: Berglund E, Stern J, Alonso Guallart P, Chaudhry S, Kofman S, Danton M, Weiner J, Lefkowitch J, Baker S, Martinez M, Kato Y, Kato T, Sykes M, Griesemer A. Induction of Mixed Chimerism to Prolong Liver Allograft Survival in Cynomolgus Monkeys. Am J Transplant. 2017;17 (suppl 3).
To cite this abstract in AMA style:Berglund E, Stern J, Guallart PAlonso, Chaudhry S, Kofman S, Danton M, Weiner J, Lefkowitch J, Baker S, Martinez M, Kato Y, Kato T, Sykes M, Griesemer A. Induction of Mixed Chimerism to Prolong Liver Allograft Survival in Cynomolgus Monkeys. [abstract]. Am J Transplant. 2017; 17 (suppl 3). https://atcmeetingabstracts.com/abstract/induction-of-mixed-chimerism-to-prolong-liver-allograft-survival-in-cynomolgus-monkeys/. Accessed August 15, 2020.
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