Session Name: Biomarkers, Immune Assessment and Clinical Outcomes - I
Date: Saturday, June 5, 2021
Session Time: 4:30pm-5:30pm
Presentation Time: 5:05pm-5:10pm
*Purpose: Despite the development of highly effective immunosuppressive medications, organ rejection and the toxicity of the drugs themselves remain significant obstacles to long-term graft and patient survival. It has been known for over 5 decades that peripheral blood chimerism was associated with immunological tolerance to a transplanted organ, beginning with the observations by Owen followed by the seminal investigations by Billingham, Brent and Medawar that ultimately earned them a Nobel Prize. A major limitation to tolerance induction approaches has been the lack of a robust and reliable biomarker that would allow the safe withdrawal of immunosuppression without a high risk of organ rejection.
*Methods: Work by Ildstad and colleagues led to the discovery of the Facilitating Cell (FC), a novel CD8+TCR– bone marrow-derived cell, and the development of FCR001, an investigational allogeneic cell therapy product that could achieve chimerism and tolerance in highly HLA mismatched donor-recipient pairs, allowing for complete withdrawal of all immunosuppression without rejection.
*Results: A Phase 2 living donor kidney tolerance protocol at Northwestern and Duke Universities has achieved a 70% success rate in the ability to remove all immunosuppression therapy 12 months post-transplant in living donor transplant recipients receiving FCR001 and non-myeloablative conditioning. The therapy is successful in highly HLA mismatched related and unrelated donor-recipient pairs. Durable donor chimerism, as defined by T-cell or whole blood chimerism greater than 20% donor at 6 months post-transplant, was established in 27 subjects, 26 of whom were successfully weaned off of all immunosuppression at 1 year post-transplant.
*Conclusions: None of the 26 subjects have had kidney allograft rejection episodes or development of DSA, and all have maintained normal renal function with normal protocol biopsies over a follow-up period of 3 to 11 years post-transplant. Importantly, 1, 3, 6, and 12-month chimerism levels are highly correlated with each other and increasingly predictive over time of ability to withdraw IS at 1 year, suggesting that peripheral blood chimerism could be a valuable surrogate marker of efficacy. The present analysis explores factors influencing the time course and durability of hematopoietic chimerism in the setting of tolerance induction in living donor kidney transplantation.
To cite this abstract in AMA style:Tollerud D, Gornstein E, Leventhal J, Ravindra KV, Ildstad S. Peripheral Blood Hematopoietic Chimerism: A Robust Biomarker for Transplantation Tolerance [abstract]. Am J Transplant. 2021; 21 (suppl 3). https://atcmeetingabstracts.com/abstract/peripheral-blood-hematopoietic-chimerism-a-robust-biomarker-for-transplantation-tolerance/. Accessed June 11, 2021.
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