New therapies directed against plasma cells such as anti-CD38 antibodies and the bispecific anti–B cell maturation antigen antibodies, represent not only an important advance in the treatment of multiple myeloma but have the potential to change the treatment landscape of other antibody-mediated diseases. In solid organ transplantation, the therapeutic armamentarium targeting humoral alloimmune responses in desensitization of highly sensitized transplant candidates and posttransplant antibody-mediated rejection has lagged behind advances in preventing and treating T cell–mediated rejection. Intravenous immunoglobulin and plasmapheresis are used extensively but have limited efficacy. Currently available anti-CD20 antibodies are only partially effective in achieving B cell depletion and leaving mature plasma cells untouched. Although interleukin 6 plays an important role in the humoral alloimmune response and injury, the benefits of interleukin 6 inhibition have failed to be demonstrated in clinical trials. Even proteasome inhibitors developed specifically to target plasma cells have not fulfilled their promise, due to limited efficacy as single agents. This review focuses on the recent experience with, and potential applicability of, anti-CD38 antibodies in the field of organ transplantation and experimental data supporting their use and development for human leukocyte antigen desensitization and antibody-mediated rejection.

中文翻译：

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抗浆细胞抗体：实体器官移植中人类白细胞抗原抗体控制的新时代


针对浆细胞的新疗法，如抗 CD38 抗体和双特异性抗 B 细胞成熟抗原抗体，不仅代表了多发性骨髓瘤治疗的重要进展，而且有可能改变其他抗体介导疾病的治疗格局。在实体器官移植中，针对高度致敏移植候选物脱敏和移植后抗体介导的排斥反应中的体液同种免疫反应的治疗武器在预防和治疗 T 细胞介导的排斥反应方面落后于进展。静脉注射免疫球蛋白和血浆置换被广泛使用，但疗效有限。目前可用的抗 CD20 抗体在实现 B 细胞耗竭和未接触成熟浆细胞方面仅部分有效。尽管白细胞介素 6 在体液同种免疫反应和损伤中起重要作用，但白细胞介素 6 抑制的益处尚未在临床试验中得到证实。由于作为单一药物的疗效有限，即使是专门为靶向浆细胞开发的蛋白酶体抑制剂也未能实现其承诺。本文重点介绍了抗 CD38 抗体在器官移植领域的近期经验和潜在适用性，以及支持其用于和开发人类白细胞抗原脱敏和抗体介导排斥反应的实验数据。