ArticleEBioMedicine2020
Ex-vivo delivery of monoclonal antibody (Rituximab) to treat human donor lungs prior to transplantation.
Article in EBioMedicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 26 citations in OpenAlex.
- Emerging roles for complement in lung transplantation.The Journal of clinical investigation · 2025Review
- Permissive immunosuppression facilitates the expansion of ex vivo administered regulatory T cells in the lung allograft.Scientific reports · 2025Article
- Preclinical concept studies showing advantage of an inhaled anti-CTGF/CCN2 protein for pulmonary fibrosis treatment.Nature communications · 2025Article
- Feasibility and Safety of Ex Vivo Delivery of Rituximab to Lung Allografts in Transplant Recipients at High Risk for Epstein-Barr Virus-associated Posttransplant Lymphoproliferative Disorder.Transplantation direct · 2025Article
- The establishment of anJournal of thoracic disease · 2024Article
- Review
- B cells mediate lung ischemia/reperfusion injury by recruiting classical monocytes via synergistic B cell receptor/TLR4 signaling.The Journal of clinical investigation · 2024Article
- Ex Vivo Lung Perfusion: A Review of Current and Future Application in Lung Transplantation.Pulmonary therapy · 2022Review
- Ex-vivo lung perfusion therapies: do they add value to organ donation?Current opinion in organ transplantation · 2022Review
- Complement-targeting therapeutics for ischemia-reperfusion injury in transplantation and the potential forFrontiers in immunology · 2022Review
- Gene Therapy: Will the Promise of Optimizing Lung Allografts Become Reality?Frontiers in immunology · 2022Review
- Review
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundEx-vivo lung perfusion (EVLP) is an innovative platform for assessing donor lungs in the pre-transplant window. In this study, we demonstrate an extension of its utility by administering the anti-CD20 monoclonal antibody, Rituximab, during EVLP. We hypothesized that this would lead to targeted depletion of allograft B-cells which may provide significant clinical benefit, including the potential to reduce latent Epstein-Barr virus (EBV) and decrease the incidence of post-transplant lymphoproliferative malignancies.
methodsTwenty human donor lungs rejected for transplantation were placed on EVLP with (n = 10) or without (n = 10) 500 mg of Rituximab. Safety parameters such as lung physiology and inflammatory cytokines were evaluated. We measured the delivery efficacy through flow cytometry, immunohistochemistry and ELISA. An in-vitro culture assay, in the presence of complement, was further conducted to monitor whether B-cell depletion would occur in Rituximab-perfused samples.
findingsRituximab was successfully delivered to human lungs during EVLP as evidenced by flow cytometric binding assays where lung tissue and lymph node biopsies demonstrated occupied CD20 epitopes after perfusion with the antibody. Lymph nodes from Rituximab perfusions demonstrated a 10.9 fold-reduction in CD20+ staining compared to controls (p = 0.0003). In lung tissue, Rituximab resulted in an 8.75 fold-reduction in CD20+ staining relative to controls (p = 0.0002). This decrease in CD20+ binding illustrates the successful delivery and occupation of epitopes after perfusion with the Rituximab. No apparent safety concerns were seen as exhibited by markers associated with acute cell injury (e.g., proinflammatory cytokines), cell death (e.g., TUNEL staining), or pulmonary physiology. In a post-perfusion tissue culture model, the addition of complement (human serum) resulted in evidence of B-cell depletion consistent with what would be expected with posttransplant activation of bound Rituximab.
interpretationOur experiments illustrate the potential of EVLP as a platform to deliver monoclonal antibody therapies to treat donor lungs pretransplant with the goal of eliminating a latent virus responsible for considerable morbidity after lung transplantation.
fundingSupported by the University Health Network Transplant Center.
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