CD47 Antibody Binding Selectivity to Spare Erythrocytes

The antibody is engineered to exhibit differential binding properties: strong binding affinity to CD47 on tumor cells while showing minimal binding to CD47 on erythrocytes. This local quality differentiation is achieved through specific CDR sequence selection and antibody engineering, allowing the same antibody to have different functional effects on different cell types expressing the same antigen.

The patent utilizes camelized single domain antibodies or other antigen-binding fragments with modified effector functions (such as IgG4 isotypes with reduced complement activation). These parameter changes in antibody structure and function enable selective targeting of tumor cells while minimizing off-target effects on erythrocytes, thereby resolving the contradiction between therapeutic efficacy and safety.

The antibody demonstrates selective distribution patterns: preferential binding to tumor cells over erythrocytes. This local quality in terms of target specificity ensures that the majority of antibody molecules remain bound to tumor cells rather than being sequestered by erythrocytes, maintaining effective therapeutic concentrations at the tumor site while minimizing systemic depletion.

The patent converts the potential harm of erythrocyte binding into a benefit by engineering antibodies that specifically avoid erythrocytes. The high expression of CD47 on erythrocytes, which could be exploited as a binding target, is instead used as a selection criterion to design antibodies with explicit avoidance of this abundant tissue, thereby preventing antibody depletion and maintaining long-term therapeutic efficacy.