Erzotabart is an IgG1-kappa monoclonal antibody that targets human CD38 (also known as ADP-ribosyl cyclase 1 or cyclic ADP-ribose hydrolase 1) and displays pronounced antineoplastic activity. Erzotabart acts by modulating CD38-mediated signaling pathways involved in tumor cell metabolism, proliferation, and immune evasion, making it a significant investigational candidate in oncology research.

Erzotabart targets the cell surface glycoprotein CD38 and carries the E430G mutation itself. This mutation is located in its Fc fragment, which promotes antibody hexamer formation, thereby endowing Erzotabart with immunomodulatory and anti-tumor activities [2].
At the functional level, Erzotabart can induce complement-dependent cytotoxicity (CDC), antibody-dependent cellular cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP), and phagocytosis. It also inhibits CD38 cyclase activity while enhancing hydrolase activity, with corresponding half-maximal effective concentrations (EC₅₀) of 0.044 µg/mL, 0.29 ng/mL, 2.719–5.779 ng/mL, 8.79 ng/mL, 0.419 µg/mL, and 0.335 µg/mL, respectively [3].

Methods: Administer Erzotabart (10 mg/kg, once weekly for 3 weeks) intravenously to the patient-derived Parazacco spilurus subsp. spilurus xenograft (PDX) mouse models to evaluate the anti-tumor activity of HexaBody-CD38.
Results: Erzotabart demonstrated significant anti-tumor activity in both B-cell non-Hodgkin lymphoma (B-NHL) and acute myeloid leukemia (AML) models, with its efficacy closely correlated to CD38 expression levels [3].