Induction of Mixed Chimerism to Prolong Liver Allograft Survival in Cynomolgus Monkeys.
CCTI, Columbia University, New York, NY
Meeting: 2017 American Transplant Congress
Abstract number: 207
Keywords: Liver transplantation, Mixed chimerism, Primates, Tolerance
Session Information
Session Name: Concurrent Session: Basic Transplant Tolerance I
Session Type: Concurrent Session
Date: Monday, May 1, 2017
Session Time: 2:30pm-4:00pm
Presentation Time: 2:54pm-3:06pm
Location: E350
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 All IS was withdrawn by day 50.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
IS |
LoCD2b | Chimerism(days) | Peak chimerism | Survival(days) | Outcome |
| A(1) | 4/6 | CyA | None | 33 | 65% | 42 | Rejection |
| A(2) | 5/6 | CyA Rituximabx1 | None | 40 | 17% | 69 | Rejection |
| A(3) | Haplo | CyA Rituximabx1 | None | 22 | 21% | 57 | Rejection |
| B(1) | Full | Tacrolimus Anti-CD40
Rituximabx2 |
Day-4,-3 | >61 | 30% | 61 | Arrhythmia
No rejection |
| B(2) | 5/6 | Tacrolimus Anti-CD40
Rituximabx2 |
Day-4,-3 | >54 | 93% | 54 | GVHD
No rejection |
| C(1) | 4/6 | Tacrolimus Anti-CD40
Rituximabx1 |
Day-3,+1 | 117 | 85% | >317 | Ongoing |
| C(2) | Full | Tacrolimus Anti-CD40
Rituximabx1 |
Day-3,+1 | >77 | 93% | 77 | Pneumonia
No rejection |
| C(3) | 4/6 | Tacrolimus Anti-CD40
Rituximabx1 |
Day-3,+1 | >79 | 87% | >79 | Ongoing |
| C(4) | Haplo | Tacrolimus
Anti-CD40 Rituximabx1 |
Day-3,+1 | >25 | 33% | 25 | Sepsis |
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 November 22, 2024.« Back to 2017 American Transplant Congress