Coutance Guillaume, Chong Anita S, Habal Marlena V
Department 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.
JHLT Open. 2025 Mar 6;8:100242. doi: 10.1016/j.jhlto.2025.100242. eCollection 2025 May.
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.
同种致敏仍然是胸器官移植中的一个主要障碍，限制了移植机会，增加了等待名单上的死亡率和移植后发病率。旨在改善移植机会和降低移植后早期排斥风险的脱敏方案已经制定，但目前的策略疗效有限，需要新的策略。在对导致产生供体特异性抗体的同种免疫反应的基本原理进行综合描述之后，详细讨论了新型脱敏策略的潜力，包括抗CD38疗法、共刺激阻断和白细胞介素-6抑制作为移植前脱敏疗法，包括其使用原理、临床前和临床研究结果以及潜在的实际临床应用。还介绍了互补的新型药理学（个体化疗法、联合脱敏疗法、围手术期额外的抗体风险缓解策略）和非药理学策略（个体风险分层和免疫测定组合）。最后，简要讨论了潜在的下一代疗法（双特异性T细胞衔接器和嵌合抗原受体T细胞）以及感兴趣的临床结果。总体而言，本综述旨在提供关于这个不断发展领域的最新数据，同时牢记临床适用性，并提供使用新型移植前脱敏疗法的实际方面。
