抗CD38抗体の血液適合性アッセイへの干渉をCD38「ベイトボディ」アプローチで解決する

Blood transfusion safety depends on swift blood compatibility testing. Alloantibodies recognizing these blood group antigens determine blood compatibility, and the transfusion of incompatible blood can lead to life-threatening hemolytic transfusion reactions. Recently, the landscape of blood compatibility testing has been complicated due to the interference caused by therapeutic antibodies targeting CD38, a key target in cancer immunotherapy that is also expressed on red blood cells. The presence of anti-CD38 antibodies in blood samples has been found to bind to test or donor red blood cells, resulting in false positive tests. This interference poses a serious risk as it can potentially mask immunogenic alloantibodies and cause delays in supplying safe blood products. We present the development and application of fragment crystallizable (Fc)-fusion constructs, referred to as "baitbodies", designed to neutralize anti-CD38 antibodies and mitigate false positive test outcomes. The extracellular domain of CD38 was fused to the Fc domain of a murine immunoglobulin G. These baitbody constructs were thoroughly characterized and applied in both serological microcolumn agglutination and automated solid-phase red cell adherence assays. The CD38-mFc baitbody successfully prevented agglutination reactions induced by three clinically relevant anti-CD38 monoclonal antibodies-daratumumab, felzartamab and isatuximab-in spiked samples. This allowed the detection of alloantibodies of the Rhesus, Kell and Duffy blood groups without interference. The CD38-mFc construct also demonstrated potential in a head-to-head comparison with commercial mitigation reagents, DaraEx and Grifols sCD38. Finally, the CD38-mFc baitbody effectively neutralized daratumumab in patient samples, preventing false positive test outcomes.