For patients with organ failure, organ transplantation is one of the most effective options for treatment. Although the number of patients waiting for transplantation has steadily increased, actual transplantation operation has not increased as much. ABO-incompatible organ transplantation allows expansion of the living donor pool. Widely accepted protocol depletes B cells nonspecifically with anti-CD20 antibody. ABO-incompatible transplantation with a loss of B cell repertoire has been shown to increase the risk of microbial infection and early rejection compared to ABO-compatible transplantation. So, there is an urgent need for an alternative approach to eliminate blood group responsive B cells specifically.
Here, we described the strategy to remove ABO-responsive B cells without total depletion of B cells. We designed a bispecific antibody that recruits T cells to ABO reactive B cells. We conjugated synthetic blood group antigens containing various lengths and valency to T cell recruiting anti-CD3 Fab. Through biochemical assays, we selected an effective candidate molecule. We then showed that the recruited T cells effectively eradicate the responsive B cells in a bispecific antibody dependent manner in vivo. Our platform suggests an availability to target and remove carbohydrate antigen recognizing B cells, specifically. Also, result implies further clues to substitute pan-B cell depletion in ABO-incompatible transplantation.