Postdoctoral Research Fellow Columbia University/Columbia Center for Translational Immunology New York, New York, United States
Abstract Text: Several tolerance protocols in pre-clinical models and clinical transplantation rely on peripheral T cell depletion and thymic irradiation to reduce donor-reactive T cells during the peri-transplantation period. Decreasing toxicity of these protocols would facilitate broader clinical application. A novel anti-CD5 antibody-drug conjugate (anti-CD5ADC) with a short half-life has been shown to be effective for peripheral T cell and thymocyte depletion in humanized mice. This study examines the efficacy and toxicity of anti-CD5ADC in a pre-clinical NHP model. Six macaques underwent hemisternotomy for thymic biopsy on day -10. Five animals were administered 2 mg/kg of anti-CD5ADC on day 0. A control animal did not receive the drug. Animals were euthanized on day 4. CBC, BMP and LFTs were measured daily. Cell counts per gram of thymic tissue were used to quantify thymocytes. Flow cytometry was used to characterize lymphocyte populations in the blood and thymus. The drug was well tolerated aside from mild, asymptomatic LFT elevations. The average percent reduction in thymocytes was 55.27% for experimental animals vs 14.99% for the control. Paired t-tests for reduction in thymocytes/gram demonstrated a p-value of 0.0567 for experimental animals. The average peripheral CD3+ count was 4147.30 cells/uL blood on day 0, declining to 244.62 on day 4 for treated animals. Memory and naïve T cell subsets were similarly depleted. The anti-CD5ADC is safe and effective at peripheral and thymic lymphocyte depletion and warrants further studies for its efficacy as a replacement for thymic irradiation and chemical T cell depleting agents in NHP tolerance models.
