Dostarlimab

Approximately 13-30% of recurrent endometrial cancers involve microsatellite instability (MSI) or mismatch repair deficiency (dMMR). The mutations resulting in dMMR endometrial cancers are primarily somatic in nature (~90%), although 5-10% of cases involve germline mutations. Cancers that have mutations resulting in dMMR can upregulate the expression of programmed death receptor-1 (PD-1) ligands 1 and 2 (PD-L1 and -L2) - PD-1 is found on T-cells and, when activated, inhibits their proliferation and the production of cytokines. The binding of these ligands to PD-1 thereby functions as an immune checkpoint that downregulates the anti-tumor immune response.

Dostarlimab is a monoclonal antibody targeted against PD-1 - it binds to the receptor and prevents interactions with PD-L1 and PD-L2, thus allowing the anti-tumor immune response to proceed unimpeded.