anti-CD73 monoclonal antibody HB0045

A compound preparation composed of two monoclonal antibodies, HB0038 and HB0039, targeting different epitopes of human ectoenzyme 5'-ecto-nucleotidase (cluster of differentiation 73; CD73; 5'-NT; ecto-5'-nucleotidase; NT5E), in a 1:1 molar ratio, with potential immunomodulating and antineoplastic activities. Upon administration, anti-CD73 monoclonal antibody HB0045 targets and binds to two different epitopes of CD73 on tumor cells. HB0038 specifically binds to the catalytic domain composed of the N-terminus and C-terminus of CD73, thereby sterically blocking the CD73-mediated conversion of extracellular adenosine monophosphate (AMP) to adenosine. HB0039 specifically and allosterically binds to the N-terminal region of CD73, thereby inhibiting the transition of CD73 from the inactive "open" conformation to a catalytically active "closed" conformation. This inhibits its enzymatic activity and further prevents adenosine formation from AMP. This prevents adenosine-mediated suppression of lymphocyte activity and increases the activity of cytotoxic T lymphocytes (CTLs). This also 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 tumor microenvironment (TME) and promotes tumor growth.