Daratumumab and Nanobody-Based Heavy Chain Antibodies Inhibit the ADPR Cyclase but not the NAD+ Hydrolase Activity of CD38-Expressing Multiple Myeloma Cells.

ABSTRACT: The nucleotides ATP and NAD+ are released from stressed cells as endogenous danger signals. Ecto-enzymes in the tumor microenvironment hydrolyze these inflammatory nucleotides to immunosuppressive adenosine, thereby, hampering anti-tumor immune responses. The NAD+ hydrolase CD38 is expressed at high levels on the cell surface of multiple myeloma (MM) cells. Daratumumab, a CD38-specific monoclonal antibody promotes cytotoxicity against MM cells. With long CDR3 loops, nanobodies and nanobody-based heavy chain antibodies (hcAbs) might bind to cavities on CD38 and thereby inhibit its enzyme activity more potently than conventional antibodies. The goal of our study was to establish assays for monitoring the enzymatic activities of CD38 on the cell surface of tumor cells and to assess the effect

SUBMITTER: Baum N 

PROVIDER: S-EPMC7795599 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature