Desensitization With Proteasome Inhibition and Costimulation Blockade Modulates the Xenoreactive Humoral Response in Nonhuman Primate Xenotransplantation.

ABSTRACT:

Introduction

"Delayed" antibody-mediated xenograft rejection is one of the most important obstacles to clinical application of pig organ xenografts. The aim of this study was to assess the impact of a structured desensitization regimen including proteasome inhibition and next-generation costimulation blockade on xenoreactive antibodies.

Methods

Rhesus macaques with moderate-high pre-treatment xenoreactive antibody titers (N = 2) were selected. Recipients received twice-weekly carfilzomib (20 mg/m²), anti-CD154 (20 mg/kg) every other week, and CD4 and CD20 lymphocyte cell depletion. Bone marrow was acquired to assess plasma cell depletion in response to proteasome inhibition. A flow cytometry-based xenoreactive crossmatch assay was performed to assess levels of cir

SUBMITTER: Lovasik BP 

PROVIDER: S-EPMC12012413 | biostudies-literature | 2025 Mar-Apr

REPOSITORIES: biostudies-literature