Cluster of differentiation 38 (CD38) (CD38)

Cluster of differentiation 38 (CD38) is a multifunctional transmembrane glycoprotein that acts as both a cell surface receptor and an enzyme involved in the metabolism of nicotinamide adenine dinucleotide (NAD+) (UniProt, 2024). It is highly and uniformly expressed on multiple myeloma cells, making it a primary therapeutic target in hematologic malignancies (Martin et al., 2019). The term "Fc region of isatuximab-opsonized cells" specifically refers to the state where the monoclonal antibody isatuximab has bound to CD38 on the target cell surface (FDA, 2020). In this state, the antibody's Fc region is exposed to recruit immune effector cells, such as natural killer (NK) cells and macrophages, through their Fc gamma receptors (FcγRs) (Moreau et al., 2016). This recruitment triggers potent anti-tumor effector functions, including antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP), which are central to the drug's clinical efficacy (Deckert et al., 2014). Additionally, isatuximab binding can directly induce apoptosis and inhibit the enzymatic activity of CD38, further contributing to its therapeutic effect (Martin et al., 2019).

Other names

ADP-ribosyl cyclase 1 (UniProt, 2024)Cyclic ADP-ribose hydrolase 1 (UniProt, 2024)T10 (UniProt, 2024)cADPr hydrolase 1 (UniProt, 2024)

Isatuximab binds to a specific epitope on the CD38 receptor, opsonizing the cell and allowing its Fc region to engage Fc gamma receptors on effector cells to induce ADCC and ADCP; it also induces direct apoptosis and inhibits CD38 enzymatic activity (FDA, 2020; Martin et al., 2019).