Session Time: 10:30am-11:30am
Presentation Time: 11:00am-11:10am
*Purpose: Infiltration of CD8 T cells into solid organ grafts is an early sign of rejection. REGN5054 is a fully human monoclonal antibody that binds specifically to human and cynomolgus T cell CD8. When radiolabeled with 89Zr, REGN5054 immuno-PET is a non-invasive method that may detect early graft rejection.
*Methods: REGN5054 was conjugated to the bifunctional chelator p-SCN-Bn-deferoxamine (DFO) for 89Zr radiolabeling to generate 89Zr-DFO-REGN5054. 4 cynomolgus macaques underwent induction with splenectomy, rituximab, mycophenolate-mofetil, tacrolimus, steroids, and orthotopic kidney transplantation. The contralateral, naïve kidney served as control. An initial phase of immunosuppression (IS) was followed by a phase of simulated graft rejection by tapering down IS, and a phase of rescue by tapering up IS. At the end of each phase, antibody was injected and immuno-PET/CT images followed Day1 and Day4. Graft kidney biopsies and ultrasound were performed and plasma samples collected for immunogenicity and PK analysis.
*Results: 89Zr-DFO-REGN5054 showed low uptake in both graft and native kidneys during pre-rejection. Increased uptake was detected in the graft during rejection by immuno-PET (Figure 1), correlating with histologic lymphocyte infiltration and increased resistance indices in ultrasound (Figure 2). Post-rejection, uptake in the kidney grafts was incompletely reduced compared to the rejection phase, while the uptake in the native kidney remained similar.
*Conclusions: Anti-CD8 Immuno-PET is a sensitive, non-invasive tool to track early graft rejection.
To cite this abstract in AMA style:Bruestle K, Tavare R, Fredriksson F, Duggan E, Huang F, Bhola B, Giurleo J, Foster R, Krueger P, Dobosz M, Ekanayake-Alper D, Sakai H, Piegari B, Castrillion J, Coley SM, Harari O, Mintz A, Ma D, Griesemer A. Anti-CD8 Immuno-PET for Non-invasive Tracking of Early Graft Rejection in a Non-human Primate Kidney Transplant Model [abstract]. Am J Transplant. 2021; 21 (suppl 3). https://atcmeetingabstracts.com/abstract/anti-cd8-immuno-pet-for-non-invasive-tracking-of-early-graft-rejection-in-a-non-human-primate-kidney-transplant-model/. Accessed July 24, 2021.
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