Inhibition of cytomegalovirus reactivation by ex vivo treatment of human kidneys with the SYN002 immunotoxin.

Human cytomegalovirus (HCMV) is a ubiquitous pathogen that establishes latent infections, with no accompanying disease. However, during immune suppression, eg, during organ transplantation, the virus can reactivate and cause serious morbidity. SYN002 is a chemokine-based immunotoxin targeting HCMV protein "Unique Short 28," a virally encoded receptor expressed on both latently and lytically HCMV-infected cells. Following binding to and internalization through the HCMV protein "Unique Short 28," SYN002 induces apoptosis of the infected cell. The feasibility and safety of delivering SYN002 to human kidneys during normothermic machine perfusion to target HCMV were investigated. Cells from treated kidneys were isolated and analyzed in HCMV reactivation assays to quantify the latent viral reservoir. Perfusate parameters, perfusate, urine, and tissue samples were also collected for assessment of kidney function and injury. Administration of SYN002 significantly reduced the level of HCMV in kidneys, with no such decrease in control kidneys. There was no significant difference in perfusion parameters, urine output, injury markers, or histopathology between treated and control kidneys. SYN002 treatment during normothermic machine perfusion appeared safe and reduced HCMV levels in cells isolated from kidney perfusates. The study provides compelling proof-of-concept that SYN002 is efficacious and safe and that the use of SYN002 in this setting can be expected to provide clinical benefit.