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  1. Article ; Online: Novel approaches for long-term lung transplant survival.

    Miller, Cynthia L / O, Jane M / Allan, James S / Madsen, Joren C

    Frontiers in immunology

    2022  Volume 13, Page(s) 931251

    Abstract: Allograft failure remains a major barrier in the field of lung transplantation and results primarily from acute and chronic rejection. To date, standard-of-care immunosuppressive regimens have proven unsuccessful in achieving acceptable long-term graft ... ...

    Abstract Allograft failure remains a major barrier in the field of lung transplantation and results primarily from acute and chronic rejection. To date, standard-of-care immunosuppressive regimens have proven unsuccessful in achieving acceptable long-term graft and patient survival. Recent insights into the unique immunologic properties of lung allografts provide an opportunity to develop more effective immunosuppressive strategies. Here we describe advances in our understanding of the mechanisms driving lung allograft rejection and highlight recent progress in the development of novel, lung-specific strategies aimed at promoting long-term allograft survival, including tolerance.
    MeSH term(s) Graft Rejection ; Humans ; Immune Tolerance ; Immunosuppressive Agents ; Lung Transplantation ; Transplantation, Homologous
    Chemical Substances Immunosuppressive Agents
    Language English
    Publishing date 2022-07-27
    Publishing country Switzerland
    Document type Journal Article ; Review ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2022.931251
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: A Mixed-chimerism Protocol Utilizing Thymoglobulin and Belatacept Did Not Induce Lung Allograft Tolerance, Despite Previous Success in Renal Allotransplantation.

    Sommer, Wiebke / O, Jane M / Pruner, Kurt B / Dehnadi, Abbas / Ha Huh, Kyu / Robinson, Kortney A / Hanekamp, Isabel / Rosales, Ivy / Bean, Alison S / Paster, Josh / Oura, Tetsu / Neal Smith, Rex / Colvin, Robert / Benichou, Gilles / Kawai, Tatsuo / Madsen, Joren C / Allan, James S

    Transplantation direct

    2021  Volume 7, Issue 6, Page(s) e705

    Abstract: Background: In kidney transplantation, long-term allograft acceptance in cynomolgus macaques was achieved using a mixed-chimerism protocol based on the clinically available reagents, rabbit anti-thymocyte globulin (ATG), and belatacept. Here, we have ... ...

    Abstract Background: In kidney transplantation, long-term allograft acceptance in cynomolgus macaques was achieved using a mixed-chimerism protocol based on the clinically available reagents, rabbit anti-thymocyte globulin (ATG), and belatacept. Here, we have tested the same protocol in cynomolgus macaques transplanted with fully allogeneic lung grafts.
    Methods: Five cynomolgus macaques underwent left orthotopic lung transplantation. Initial immunosuppression included equine ATG and anti-IL6RmAb induction, followed by triple-drug immunosuppression for 4 mo. Post-transplant, a nonmyeloablative conditioning regimen was applied, including total body and thymic irradiation. Rabbit ATG, belatacept, anti-IL6RmAb, and donor bone marrow transplantation (DBMT) were given, in addition to a 28-d course of cyclosporine. All immunosuppressant drugs were stopped on day 29 after DBMT.
    Results: One monkey rejected its lung before DBMT due to AMR, after developing donor-specific antibodies. Two monkeys developed fatal post-transplant lymphoproliferative disorder, and both monkeys had signs of cellular rejection in their allografts upon autopsy. The remaining 2 monkeys showed severe cellular rejection on days 42 and 70 post-DBMT. Cytokine analysis suggested higher levels of pro-inflammatory markers in the lung transplant cohort, as compared to kidney recipients.
    Conclusion: Although the clinically applicable protocol showed success in kidney transplantation, the study did not show long-term survival in a lung transplant model, highlighting the organ-specific differences in tolerance induction.
    Language English
    Publishing date 2021-05-25
    Publishing country United States
    Document type Journal Article
    ISSN 2373-8731
    ISSN 2373-8731
    DOI 10.1097/TXD.0000000000001150
    Database MEDical Literature Analysis and Retrieval System OnLINE

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