*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.

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