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Vashti Lacaille, Michael Kapinsky, The Nanobody JK36 circumvents the epitope overlapping commonly observed between therapeutic anti-CD38 antibodies and commercially available analytical mouse antibodies, The Journal of Immunology, Volume 206, Issue 1_Supplement, May 2021, Page 59.24, https://doi.org/10.4049/jimmunol.206.Supp.59.24
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Abstract
Therapeutic anti-CD38 antibodies have been demonstrated to elicit immune-mediated elimination of plasma cells and other CD38-expressing cells. Epitope overlapping with commercially available analytical monoclonal mouse anti-CD38 antibodies limits the possibility to study surface CD38 expression in the presence of these therapeutic antibodies. Nanobodies, derived from heavy-chain antibodies that naturally occur in llamas and other Camelids, can circumvent these undesired interferences. Nanobodies are single variable domain antibody fragments (VHH) that often expose a long complementarity-determining region 3 (CDR3). This feature allows them to recognize hidden epitopes, e.g. in molecular cavities, that are inaccessible to the CDRs in conventional analytical and therapeutic antibodies. In a model of anti-CD38 occupation with a therapeutic antibody, we have evaluated JK36, an anti-CD38 nanobody recognizing a cryptic epitope. Normal whole blood samples were pre-incubated with Daratumumab, a therapeutic humanized anti-CD38 mouse antibody. Binding of the Rabbit-JK36 (Rb-JK36) construct was compared to the binding observed with the conventional mouse antibodies, clones LS198-4-3 and T16. LS198-4-3 and T16 antibodies partially or completely failed to label the CD38 epitope, in case of being masked with Daratumumab. In contrast, the Rb-JK36 staining pattern and intensity remained unchanged, confirming that Rb-JK36 binds to an epitope which is not masked by Daratumumab. This study confirms that JK36 is a well-suited probe for research studies on CD38 expression in the presence of therapeutic or commonly used analytical anti-CD38 antibodies, opening new methodical approaches in plasma cell immunotherapy research.
