Transplant research in nonhuman primates to evaluate clinically relevant immune strategies in organ transplantation

Abstract

Research in transplant immunology using non-human primate (NHP) species to evaluate immunologic strategies to prevent rejection and prolong allograft survival has yielded results that have translated successfully into human organ transplant patient management. Other therapies have not proceeded to human translation due to failure in NHP testing, arguably sparing humans the futility and risk of such testing. The NHP transplant models are ethically necessary for drug development in this field and provide the closest analogue to human transplant patients available. The refinement of this resource with respect to colony MHC typing, reagent and assay development, and availability to the research community has greatly enhanced knowledge about transplant immunology and drug development.

Allo-Specific Humoral Responses: New Methods for Screening Donor-Specific Antibody and Characterization of HLA-Specific Memory B Cells

“…Non-human primates offer an important experimental model to develop novel therapies for clinical translation ( 39 ). Attempts to use HLA-specific SAB reagents to characterize NHP alloantibody responses have been made ( 40 ), albeit with limited resolution of specificity. In most NHP research, therefore, the standard assay for alloantibody detection relies on a donor-cell antibody capture method analogous to the flow cytometric crossmatch used in clinical transplantation ( 12 , 41 , 42 ).…”

Experimental modeling of desensitization: What have we learned about preventing AMR?

“…The nonhuman primate (NHP) Transplantation Tolerance Cooperative Study Group has been actively working on developing and evaluating new immunosuppressive agents/strategies using NHP models of kidney, heart, islet, pancreatic, and lung transplant since 1999 (extensive reviews are available 4,5 ). Initially, however, the humoral component of rejection in organ transplant was regarded as a peripheral issue not addressed by early NHP studies.…”

“…NHP models provide valuable resources for the testing of potentially clinically translatable approaches in organ transplant. The similarities between NHPs and humans have made the NHP a desirable model for the study of many immunopathologic diseases, including organ transplant 4,5 . The NHP model contains a few important benefits (reviewed extensively 78,79 and here earlier).…”

Non-human Primate Regulatory T Cells and Their Assessment as Cellular Therapeutics in Preclinical Transplantation Models

“…In addition, whereas MHC class II Ags that are key to induction of alloimmunity are absent from rodent vascular endothelium, they are expressed constitutively by these cells in large animals ( Choo et al, 1997 ; Houser et al, 2004 ). Due to (i) similarities between NHP and human immune systems, (ii) cross-reactivity between drug targets in these species, (iii) the outbred nature of NHP, (iv) their natural exposure to environmental pathogens, and (v) their longevity compared with mice, NHP are important models for studying mechanisms underlying immune regulation and tolerance ( Fitch et al, 2019 ). NHP also allow evaluation of the scalability and safety of innovative therapeutic strategies (e.g., monitoring and management of adverse events, such as potential infusion reactions and infectious complications) and associated techniques, e.g., leukapheresis in conjunction with cell therapy, that are not practiced in rodents.…”