This invention comprises novel anti-CD73 monoclonal antibody compositions that recognize and inhibit mouse and human CD73.
CD73, an ecto-enzyme associated with adenosine metabolism, is an emerging immune checkpoint that promotes tumor progression by suppressing antitumor immune responses and promoting angiogenesis. Its expression is commonly elevated in human solid tumors, correlating with invasiveness and metastasis, and therefore, poor prognosis and therapy resistance. CD73, along with other adenosinergic molecules, play key roles in fostering an immunosuppressive tumor microenvironment by affecting multiple types of immune cells, including immune suppressor cells and immune effector cells. Accumulating data reveal that the combination of anti-CD73 and/or inhibitors targeting adenosine receptor A2AR with immune checkpoint blockade has promising clinical activity in patients with advanced solid tumors.
The anti-CD73 monoclonal antibody, termed E7, binds to and inhibits both human and murine CD73. Data from experiments conducted during development demonstrate that E7 overcomes TGF-β-mediated inhibitory effect on murine CD8+ T cell responses and human CAR T cell polyfunctionality in vitro, which is superior to other available anti-CD73 mAbs. Preclinical studies also demonstrate that E7 significantly improves the survival of ovarian tumor-bearing mice, showcasing its potential as a therapeutic tool in cancer treatment, particularly when combined with other immunotherapies.
E7 increases survival of ID8 ovarian tumor-bearing mice. ID8 ovarian tumor-bearing C57BL/6 mice were treated with control IgG or E7. Survival curves for treated group and control group. Shown are 8 mice per group. Data are represented as mean ± SEM (*p=0.0326).