Definition

A monoclonal antibody targeting the ectoenzyme 5′-ecto-nucleotidase (cluster of differentiation 73; CD73; 5′-NT; ecto-5′-nucleotidase; NT5E), with potential immunomodulating and antineoplastic activities. Upon administration, anti-CD73 monoclonal antibody IBI325 targets and binds to CD73 on tumor cells, thereby inhibiting the activity of CD73. This prevents CD73-mediated conversion of extracellular adenosine monophosphate (AMP) to adenosine and the adenosine-mediated suppression of lymphocyte activity and trafficking. This attenuates the adenosine-induced immunosuppression in tumor microenvironment (TME), increases the activity of cytotoxic T lymphocytes (CTLs), activates macrophages and reduces the activity of both myeloid-derived suppressor cells (MDSCs) and regulatory T lymphocytes (Tregs). By abrogating the inhibitory effect on the immune system and enhancing the CTL-mediated immune response against cancer cells, tumor cell growth is decreased. CD73, a plasma membrane protein belonging to the 5′-nucleotidase (NTase) family, is upregulated on a number of cancer cell types and catalyzes the conversion of extracellular nucleotides, such as AMP, to membrane-permeable nucleosides, such as adenosine; it plays a key role in adenosine-mediated immunosuppression within the TME.