Definition

A monoclonal antibody directed against ectonucleoside triphosphate diphosphohydrolase 2 (ENTPD2), with potential immunomodulating and antineoplastic activities. Upon administration, anti-ENTPD2 monoclonal antibody KAZ954 targets and binds to ENTPD2 expressed on a variety of tumor cells and inhibits its hydrolase activity, thereby preventing the conversion of adenosine triphosphate (ATP) to adenosine diphosphate (ADP). This leads to an increased intra-tumoral ATP:ADP ratio, an increase in intra-tumoral monocytes, natural killer (NK) cells, peripheral CD8+ T cells, macrophages, and CD11b+ dendritic cells (DCs), and results in a systemic pro-inflammatory response in the tumor microenvironment (TME). In addition, KAZ954 induces antibody-dependent cellular cytotoxicity (ADCC) in ENTPD2-overexpressing tumor cells. ENTPD2 catalyzes the hydrolysis of ATP, reduces the cytotoxic antitumor immune response, enhances the proliferation and polarization of immunosuppressive cells, and increases neovascularization. It plays a key role in the creation of an immunosuppressive TME.