Not all anti-CD38 antibodies are created equal: The epitope of felzartamab is partially DTT-resistant.

Authors

Anja Zeretzke, Philipp Trummer, Cora P Habicht, Clemens Schneeweiss

Published in

Transfusion medicine (Oxford, England). Sep 02, 2026. Epub Sep 02, 2026.

Abstract

To evaluate anti-CD38 antibody candidates for their ability to bind to DTT-treated CD38 and red blood cells (RBCs).
Dithiothreitol (DTT) treatment of RBCs is routinely used to denature CD38 and mitigate interference from anti-CD38 antibodies, such as daratumumab and isatuximab, in immunohematology testing. However, new anti-CD38 antibodies are in development, some of which may be directed against linear or otherwise DTT-resistant epitopes.
Anti-CD38 antibody candidates were titrated in an enzyme-linked immunosorbent assay (ELISA) to assess their ability to bind to untreated and DTT-treated recombinant CD38. Antibody binding was subsequently confirmed by flow cytometry of RBCs. Daratumumab and felzartamab were then tested on a panel of native and DTT-treated RBCs in the indirect antiglobulin test (IAT).
All antibodies except felzartamab failed to bind to DTT-denatured CD38 in ELISA at concentrations up to 1.25 μg/mL. Flow cytometry confirmed this binding pattern. In the IAT, some DTT-treated cells remained positive with felzartamab, despite being negative with daratumumab.
Not all epitopes of anti-CD38 antibodies are fully DTT-sensitive. This has important implications for handling of anti-CD38 antibody induced interference in immunohematology, and raises the question of whether DTT is an adequate solution for interference mitigation.

PMID:
42683597
Bibliographic data and abstract were imported from PubMed on 02 Sep 2026.

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