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Transplant tolerance in non-human primates: progress, current challenges and unmet needs
L S Kean1, S Gangappa, T C Pearson
1Emory Transplant Center, Department of Surgery, Emory University School of Medicine, Atlanta, GA, USA.
Summary
Inducing immune tolerance after organ transplantation remains crucial. This review examines four key strategies in non-human primates, highlighting challenges and future directions for clinical application.
Area of Science:
- Transplantation immunology
- Immunosuppression
- Tolerance induction
Background:
- Current immunosuppressive regimens post-organ transplant cause significant morbidity.
- Translating murine models of tolerance induction to clinical practice faces barriers.
- Non-human primates (NHP) serve as a critical pre-clinical model for transplantation research.
Purpose of the Study:
- To review prominent strategies for inducing transplantation tolerance.
- To evaluate the success and limitations of these strategies in NHP models.
- To identify unmet needs and barriers in clinical tolerance induction.
Main Methods:
- Review of four primary strategies for tolerance induction.
- Analysis of their efficacy and shortcomings in non-human primate studies.
- Identification of current challenges and future research directions.
Main Results:
- T-cell costimulation blockade shows promise but requires further refinement.
- Mixed chimerism induction presents engraftment challenges in NHP.
- T-cell depletion strategies necessitate careful management of infection risks.
- Regulatory T-cell based therapies demonstrate potential but face hurdles in stability and expansion.
Conclusions:
- Significant progress has been made in NHP models for tolerance induction.
- Barriers remain in translating these strategies to human clinical transplantation.
- Further research is needed to overcome unmet needs for successful clinical tolerance induction.