Novel pretransplant desensitization strategies in heart transplantation

Allosensitization remains a major barrier in thoracic organ transplantation, limiting access to transplantation and increasing waitlist mortality and post-transplant morbidity. Desensitization protocols aimed at improving access to transplantation and mitigating the risk of early post-transplant rej...

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Main Authors: Guillaume Coutance, MD, PhD, Anita S. Chong, PhD, Marlena V. Habal, MD
Format: Article
Language:English
Published: Elsevier 2025-05-01
Series:JHLT Open
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Online Access:http://www.sciencedirect.com/science/article/pii/S2950133425000370
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author Guillaume Coutance, MD, PhD
Anita S. Chong, PhD
Marlena V. Habal, MD
author_facet Guillaume Coutance, MD, PhD
Anita S. Chong, PhD
Marlena V. Habal, MD
author_sort Guillaume Coutance, MD, PhD
collection DOAJ
description Allosensitization remains a major barrier in thoracic organ transplantation, limiting access to transplantation and increasing waitlist mortality and post-transplant morbidity. Desensitization protocols aimed at improving access to transplantation and mitigating the risk of early post-transplant rejection have been developed, but current strategies have limited efficacy, and new strategies are needed. After a synthetic description of the basics of alloimmune responses leading to the production of donor-specific antibodies, the potential of novel desensitization strategies, including anti-CD38 therapies, costimulation blockade, and interleukin-6 inhibition as pretransplant desensitization therapies, are discussed in detail, including the rationale for their use, results of preclinical and clinical studies, and potential practical clinical application. Complementary novel pharmacologic (individualization therapies, combination desensitization therapies, additional perioperative antibody-risk mitigation strategies) and nonpharmacologic strategies (individual risk stratification and combination of immunologic assays) are also presented. Finally, potential next-generation therapies (bispecific T-cell engager and chimeric antigen receptor T cells) and clinical outcomes of interest are briefly discussed. Overall, this review aims to provide recent data on this constantly evolving field, while keeping in mind the clinical applicability and providing practical aspects of the use of novel pretransplant desensitization therapies.
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spelling doaj-art-856f06aa164f4f1dbe45e45b6a8b63ad2025-08-20T03:48:50ZengElsevierJHLT Open2950-13342025-05-01810024210.1016/j.jhlto.2025.100242Novel pretransplant desensitization strategies in heart transplantationGuillaume Coutance, MD, PhD0Anita S. Chong, PhD1Marlena V. Habal, MD2Department of Cardiac and Thoracic Surgery, Cardiology Institute, Pitié Salpêtrière Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), Sorbonne University Medical School, Paris, France; Paris Translational Research Centre for Organ Transplantation, INSERM, UMR-S970, University Paris Cité, Paris, France; Corresponding author: Guillaume Coutance, MD, PhD, Service de Chirurgie Cardiaque, GH Pitié-Salpêtrière, 56, Bd Vincent Auriol, 75013 Paris, France.Department of Surgery, University of Chicago, Chicago, IllinoisDivision of Cardiology, Department of Medicine, New York University, Grossman School of Medicine, New York, New YorkAllosensitization remains a major barrier in thoracic organ transplantation, limiting access to transplantation and increasing waitlist mortality and post-transplant morbidity. Desensitization protocols aimed at improving access to transplantation and mitigating the risk of early post-transplant rejection have been developed, but current strategies have limited efficacy, and new strategies are needed. After a synthetic description of the basics of alloimmune responses leading to the production of donor-specific antibodies, the potential of novel desensitization strategies, including anti-CD38 therapies, costimulation blockade, and interleukin-6 inhibition as pretransplant desensitization therapies, are discussed in detail, including the rationale for their use, results of preclinical and clinical studies, and potential practical clinical application. Complementary novel pharmacologic (individualization therapies, combination desensitization therapies, additional perioperative antibody-risk mitigation strategies) and nonpharmacologic strategies (individual risk stratification and combination of immunologic assays) are also presented. Finally, potential next-generation therapies (bispecific T-cell engager and chimeric antigen receptor T cells) and clinical outcomes of interest are briefly discussed. Overall, this review aims to provide recent data on this constantly evolving field, while keeping in mind the clinical applicability and providing practical aspects of the use of novel pretransplant desensitization therapies.http://www.sciencedirect.com/science/article/pii/S2950133425000370heart transplantationdesensitizationantibody-mediated rejectionimmunosuppressionimmunology
spellingShingle Guillaume Coutance, MD, PhD
Anita S. Chong, PhD
Marlena V. Habal, MD
Novel pretransplant desensitization strategies in heart transplantation
JHLT Open
heart transplantation
desensitization
antibody-mediated rejection
immunosuppression
immunology
title Novel pretransplant desensitization strategies in heart transplantation
title_full Novel pretransplant desensitization strategies in heart transplantation
title_fullStr Novel pretransplant desensitization strategies in heart transplantation
title_full_unstemmed Novel pretransplant desensitization strategies in heart transplantation
title_short Novel pretransplant desensitization strategies in heart transplantation
title_sort novel pretransplant desensitization strategies in heart transplantation
topic heart transplantation
desensitization
antibody-mediated rejection
immunosuppression
immunology
url http://www.sciencedirect.com/science/article/pii/S2950133425000370
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AT marlenavhabalmd novelpretransplantdesensitizationstrategiesinhearttransplantation