Examination of Class I HLA-Fc Fusion Proteins in Targeting Cognate Antibody-Producing Cells

Human leukocyte antigen (HLA) alloimmunization poses a significant challenge in various clinical settings, including platelet refractoriness and allogeneic solid-organ and stem cell transplants. We have explored HLA-Fc fusion proteins as a novel therapeutic strategy for suppressing or reversing unwanted HLA alloimmunization. These fusion proteins, combining HLA antigen specificity with Fc-mediated cytotoxicity, show promise in targeting specific antibody-producing B cells. Initial studies using B cell hybridomas demonstrate the feasibility and selectivity of HLA-Fc in killing target cells of cognate specificities. The protocols in this chapter outline the design, production, and evaluation of HLA-Fc proteins, emphasizing their efficacy in vitro and in immunodeficient mouse models. Further research is needed to validate these findings in humanized murine alloimmunization models, potentially providing new therapeutic approaches for managing HLA-sensitized patients in clinical practice.