Factor VIII-specific B cell receptor (FVIII-specific BCR)

The Factor VIII-specific B cell receptor (FVIII-specific BCR) is a membrane-bound immunoglobulin expressed on the surface of B lymphocytes that specifically recognize and bind to exogenous Factor VIII (FVIII) (Scott et al., 2021). In patients with Hemophilia A, the development of neutralizing alloantibodies, known as inhibitors, against replacement FVIII therapy is a significant clinical challenge, occurring in approximately 30% of patients with severe disease (Zhang et al., 2016). These inhibitors are produced by plasma cells derived from B cells that have been activated via their FVIII-specific BCRs. Therapeutic targeting of these BCRs aims to selectively deplete the pathogenic B cell clones without causing broad immunosuppression. Experimental approaches include B-cell Antibody Receptor (BAR) T cells, which are engineered to express FVIII domains that bind directly to the BCR, triggering the destruction of the target B cell (Parvathaneni et al., 2021). This precision approach is designed to eradicate the source of inhibitors and restore the efficacy of FVIII replacement therapy.

Other names

Anti-FVIII B-cell receptorFactor VIII inhibitor B-cell receptorFVIII-specific BCRB-cell receptor for Factor VIII

Selective depletion of B cells expressing the Factor VIII-specific receptor through targeted cytotoxicity mediated by engineered T cells or induction of immune tolerance via antigen-specific interactions.