ADP-ribosyl cyclase 1 (CD38) (CD38)

ADP-ribosyl cyclase 1 (CD38) is a multifunctional type II transmembrane glycoprotein that serves as both an ectoenzyme and a cell surface receptor [1, 5]. It is primarily involved in the metabolism of nicotinamide adenine dinucleotide (NAD+), catalyzing the production of second messengers like cyclic ADP-ribose (cADPR) which are essential for intracellular calcium mobilization [1, 2]. CD38 is expressed at low levels on various lymphoid and myeloid cells but is highly and uniformly overexpressed on malignant plasma cells in multiple myeloma, making it a critical therapeutic target [4, 5]. Therapeutic agents targeting CD38, such as daratumumab and the immunocytokine modakafusp alfa, utilize mechanisms including antibody-dependent cellular cytotoxicity (ADCC) and the targeted delivery of attenuated interferon-alpha to induce apoptosis in cancer cells [3, 4]. Beyond oncology, CD38 is increasingly recognized for its role in age-related NAD+ decline and chronic inflammatory conditions [5].

Other names

ADP-ribosyl cyclase 1Cyclic ADP-ribose hydrolase 1T10ADPRC 1Cluster of Differentiation 38

Targeted depletion of CD38-positive cells via antibody-dependent cellular cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP), and complement-dependent cytotoxicity (CDC) [4]. For immunocytokines like modakafusp alfa, the mechanism involves the targeted delivery of attenuated interferon-alpha to CD38-expressing cells, triggering pro-apoptotic and anti-proliferative signaling through the interferon-alpha/beta receptor (IFNAR) [3].