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Published on: March 5, 2012
Resolving the Interference of Anti-CD38 Antibodies on Blood Compatibility Assays Using CD38 "Baitbodies" Approach.
Dianne Celine Gnann1, Stephan Steinke1, Hendrikus S P Garritsen2,3
1Abteilung Medizinische Biotechnologie, Institut für Biochemie, Biotechnologie und Bioinformatik, Technische Universität Braunschweig, Braunschweig, 38106, Germany, tu-braunschweig.de.
New baitbody constructs neutralize anti-CD38 antibodies, preventing false positives in blood compatibility testing. This innovation ensures safer blood transfusions by eliminating interference from cancer immunotherapy drugs.
Area of Science:
- Immunology
- Transfusion Medicine
- Biotechnology
Background:
- Blood transfusion safety relies on accurate compatibility testing to prevent hemolytic reactions.
- Therapeutic anti-CD38 antibodies, used in cancer immunotherapy, interfere with blood testing by causing false positives.
- This interference can mask clinically significant alloantibodies, delaying safe blood product availability.
Purpose of the Study:
- To develop and validate novel Fc-fusion constructs, termed "baitbodies", to neutralize anti-CD38 antibodies.
- To mitigate interference in blood compatibility testing caused by anti-CD38 antibodies.
- To ensure the reliable detection of alloantibodies in the presence of anti-CD38 therapies.
Main Methods:
- Engineered extracellular CD38 domain fused to a murine IgG Fc domain (CD38-mFc baitbody).
- Characterization and application in serological microcolumn agglutination and automated solid-phase red cell adherence assays.
- Comparative analysis against commercial reagents (DaraEx, Grifols sCD38).
Main Results:
- CD38-mFc baitbody successfully prevented false positive agglutination reactions caused by anti-CD38 monoclonal antibodies (daratumumab, felzartamab, isatuximab).
- Enabled accurate detection of Rhesus, Kell, and Duffy blood group alloantibodies in spiked samples.
- Demonstrated effective neutralization of daratumumab in patient samples, confirming its clinical utility.
Conclusions:
- Fc-fusion baitbody constructs are effective in neutralizing anti-CD38 antibodies.
- This approach significantly improves the accuracy and safety of pre-transfusion blood compatibility testing.
- Baitbodies offer a promising solution to overcome interference issues in transfusion medicine caused by targeted cancer therapies.

