Alloantibodies to human leukocyte antigens (HLA) are the leading cause of platelet refractoriness and antibody-mediated rejection of solid organ and hematopoietic stem cell grafts. These unwanted HLA antibodies may originate from prior exposure to HLA antigens, such as with previous pregnancies or transfusions, or de novo alloimmunization after exposure to antigens expressed on the transplanted cells and tissues. Clinical sequelae are challenging to treat once they develop. Platelet refractoriness can result in difficulty providing transfusion support to patients, antibody-mediated rejection of solid organs can result in organ dysfunction and/or failure, and rejection of hematopoietic stem cell transplants can result in graft failure. Existing therapies, such as therapeutic plasma exchange which removes antibodies from plasma, and rituximab, which suppresses global humoral immunity by targeting CD20+ B cells, have shown variable success. Biotherapies targeting HLA-specific antibody-producing cells are being developed. T cell-based therapies, such as chimeric antigen receptor T (CART) cells engineered to target HLA-reactive immune cells and antigen-Fc fusion protein-based biologics, are under investigation as potential therapeutic options to encourage antigen-specific and long-term immune tolerance of transplanted cells and tissues. These biotherapies may hold the promise of attenuating unwanted alloimmunization without sacrificing the protective immunity. This session will discuss the rationales of these novel approaches, present experimental evidence for their efficacy and specificity, and outline potential challenges and future directions.
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AM23-TU-10-O: Biotherapies for Targeting Unwanted Alloantibodies in Transfusion Medicine (Enduring) Evaluation