Ex vivo treatment of cytomegalovirus in human donor lungs using a novel chemokine-based immunotoxin

J Heart Lung Transplant. 2022 Mar;41(3):287-297. doi: 10.1016/j.healun.2021.10.010. Epub 2021 Oct 25.


Background: Transmission of latent human cytomegalovirus (HCMV) via organ transplantation with post-transplant viral reactivation is extremely prevalent and results in substantial adverse impact on outcomes. Therapies targeting the latent reservoir within the allograft to mitigate viral transmission would represent a major advance. Here, we delivered an immunotoxin (F49A-FTP) that targets and kills latent HCMV aiming at reducing the HCMV reservoir from donor lungs using ex-vivo lung perfusion (EVLP).

Methods: HCMV seropositive human lungs were placed on EVLP alone or EVLP + 1mg/L of F49A-FTP for 6 hours (n = 6, each). CD14+ monocytes isolated from biopsies pre and post EVLP underwent HCMV reactivation assay designed to evaluate viral reactivation capacity. Off-target effects of F49A-FTP were studied evaluating cell death markers of CD34+ and CD14+ cells using flow cytometry. Lung function on EVLP and inflammatory cytokine production were evaluated as safety endpoints.

Results: We demonstrate that lungs treated ex-vivo with F49A-FTP had a significant reduction in HCMV reactivation compared to controls, suggesting successful targeting of latent virus (76% median reduction in F49A-FTP vs 15% increase in controls, p = 0.0087). Furthermore, there was comparable cell death rates of the targeted cells between both groups, suggesting no off-target effects. Ex-vivo lung function was stable over 6 hours and no differences in key inflammatory cytokines were observed demonstrating safety of this novel treatment.

Conclusions: Ex-vivo F49A-FTP treatment of human lungs targets and kills latent HCMV, markedly attenuating HCMV reactivation. This approach demonstrates the first experiments targeting latent HCMV in a donor organ with promising results towards clinical translation.

Keywords: chemokine-based immunotoxin; ex vivo lung perfusion; human cytomegalovirus; latent cytomegalovirus; lung transplantation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chemokine CX3CL1
  • Cytomegalovirus / drug effects*
  • Cytomegalovirus Infections / drug therapy*
  • Exotoxins
  • Humans
  • Immunotoxins / pharmacology*
  • Immunotoxins / therapeutic use*
  • In Vitro Techniques
  • Lung Transplantation*
  • Patient Selection*


  • Chemokine CX3CL1
  • Exotoxins
  • F49A-FTP
  • Immunotoxins