2025-Antiplasma cell antibodies_A new era of HLA Ab 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.