Antiplasma cell antibodies: A new era of human leukocyte antigen antibody control in solid organ transplantation

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.