Anti-CD47 drug interference in pre-transfusion testing can be overcome by antigen masking.

BACKGROUND

Overexpression of CD47, a "don't eat me" signal for macrophages, in various malignancies has prompted the development of anti-CD47 therapies. Although the first-in-class anti-CD47 antibody magrolimab was abandoned due to its ineffectiveness in improving survival in acute myeloid leukemia, multiple anti-CD47 drugs remain in clinical trials. These agents can pose significant challenges in pre-transfusion diagnostics by inducing agglutination and interfering with serological testing due to CD47 expression on red blood cells.

STUDY DESIGN AND

METHODS

This study aims to evaluate the interference caused by several anti-CD47 antibodies-ligufalimab, lemzoparlimab, and letaplimab-and the SIRPα IgG1 Fc fusion protein ontorpacept in pre-transfusion testing and to compare their effects with magrolimab. We are also testing the mitigation of the anti-CD47 drug interference by antigen masking.

RESULTS

Our results show that all drugs tested significantly interfered at clinically relevant concentrations, affecting the indirect antiglobulin test and partially also card tests without anti-human globulin and Werfen's Capture-R assay. Notably, a soluble recombinant SIRPα variant, MagroEx, demonstrated efficacy in mitigating this interference in all assays tested.

DISCUSSION: These findings emphasize the need for awareness and adaptation in immunohematology practices as anti-CD47 drugs continue to advance in clinical development, and highlight the utility of antigen masking strategies to enhance the safe administration of blood products to treated patients.