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. 2025 Aug 13.
doi: 10.1111/trf.18367. Online ahead of print.

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

Cora P Habicht  1 , Svenja Adolph  1 , Daniela Grüger  1 , Rafaela Hervatin  2 , Stephan Immenschuh  2 , Jana Králová  3 , Clemens Schneeweiß  1
Affiliations

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

Cora P Habicht et al. Transfusion. .

Abstract

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.

Keywords: MagroEx; antigen masking; anti‐CD47 antibody interference; indirect antiglobulin test; pre‐transfusion testing.

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References

REFERENCES

    1. Zhang W, Huang Q, Xiao W, Zhao Y, Pi J, Xu H, et al. Advances in anti‐tumor treatments targeting the CD47/SIRPα axis. Front Immunol. 2020;11:18.
    1. Wilde L, Kasner M. Targeting CD47: many misses; hopeful for a hit. Blood. 2025;145(5):460–462.
    1. Bouwstra R, Van Meerten T, Bremer E. CD47‐SIRPα blocking‐based immunotherapy: current and prospective therapeutic strategies. Clin Transl Med. 2022;12(8):e943.
    1. Xu Y, Jiang P, Xu Z, Ye H. Opportunities and challenges for anti‐CD47 antibodies in hematological malignancies. Front Immunol. 2024;15:1348852.
    1. Dahl KN, Parthasarathy R, Westhoff CM, Layton DM, Discher DE. Protein 4.2 is critical to CD47‐membrane skeleton attachment in human red cells. Blood. 2004;103(3):1131–1136.

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