Targeting Anti-HLA Class I and II Antibodies with CAR-B Cell Therapy: A Novel Strategy to Mitigate Graft Rejection and Platelet Refractoriness

Abstract

Alloimmune responses mediated by anti-HLA (human leukocyte antigen) antibodies are significant barriers to successful transplantation and transfusion therapies. Current immunosuppressive strategies target broad components of the immune system, often leading to non-specific effects, such as increased susceptibility to infections and malignancies. Here, we propose a novel therapeutic approach using Chimeric Antigen Receptor (CAR)-B cells engineered to target anti-HLA Class I and II antibodies. By specifically neutralizing these antibodies, CAR-B cell therapy has the potential to mitigate immune responses in allogeneic transplantation and transfusion, reducing the incidence of graft rejection and transfusion reactions. It will also neutralize the T cell response by binding to reactive T cells against donor HLA molecules. In this article, we discuss the rationale, design, and anticipated outcomes of this innovative therapy.