Programmed cell death 1 ligand 1 and 5'-nucleotidase (PD-L1 / CD73)

PD-L1 / CD73 is a dual therapeutic target comprising the immune checkpoint ligand Programmed cell death 1 ligand 1 (PD-L1) and the ecto-enzyme 5'-nucleotidase (CD73). PD-L1 is frequently overexpressed on the surface of cancer cells and suppresses T-cell mediated immunity by binding to the PD-1 receptor [3, 30]. CD73 is a key enzyme in the purinergic signaling pathway that converts extracellular adenosine monophosphate (AMP) into adenosine, a metabolite that strongly inhibits the activity of cytotoxic T cells and natural killer cells [6, 10, 19]. The simultaneous blockade of these two pathways is intended to provide a synergistic anti-tumor effect by preventing T-cell exhaustion and neutralizing the immunosuppressive 'smog' of adenosine in the tumor microenvironment [1, 2, 8]. This dual-targeting approach is currently being investigated using bispecific antibodies and bifunctional small molecules, such as CC-5, to improve response rates in patients with solid tumors that are resistant to standard checkpoint inhibitors [5, 9, 12, 22]. Clinical strategies often involve the combination of PD-L1 inhibitors like durvalumab with CD73 inhibitors like oleclumab to achieve this dual blockade [2, 17].

Other names

CD274NT5EB7-H1Ecto-5'-nucleotidaseB7 homolog 1Programmed death-ligand 1

Dual blockade of the PD-1/PD-L1 immune checkpoint and the CD73-mediated adenosine immunosuppressive pathway to restore anti-tumor T-cell activity and enhance the immune response within the tumor microenvironment.