anti-CD73 monoclonal antibody PT199

A humanized monoclonal antibody directed against the human 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 PT199 targets and directly binds to an epitope that is in or near the CD73 catalytic domain, thereby non-competitively and fully inhibiting both soluble shed CD73 and membrane-bound CD73 activity. 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 the 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. PT199 may inhibit the CD73 enzyme activity by preventing the transition of CD73 from the open to the closed conformation.