Cluster of differentiation refers to an attempt to catalogue systematically a series of over 300 cell-surface proteins associated with immunotyping. Many members of the group have identified functions as enzymes (for example, see CD73 ecto-5'-nucleotidase) or receptors (for example, see CD41 integrin, alpha 2b subunit). Many CDs are targeted for therapeutic gain using antibodies for the treatment of proliferative disorders. A full listing of all the Clusters of Differentiation proteins is not possible in the Guide to PHARMACOLOGY; listed herein are selected members of the family targeted for therapeutic gain.

The endogenous ligands for human PD-1 are programmed cell death 1 ligand 1 (CD274, Q9NZQ7) (PD-L1 aka CD274) and programmed cell death 1 ligand 2 (PD-L2; PDCD1LG2). These ligands are cell surface peptides, normally involved in immune system regulation. Expression of PD-1 by cancer cells induces immune tolerance and evasion of immune system attack [18]. Anti-PD-1 monoclonal antibodies are used to induce immune checkpoint blockade as a therapeutic intervention in cancer, effectively re-establishing immune vigilance. Pembrolizumab was the first anti-PD-1 antibody to be approved by the US FDA.

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* Huang MY, Jiang XM, Wang BL, Sun Y, Lu JJ. (2021) Combination therapy with PD-1/PD-L1 blockade in non-small cell lung cancer: strategies and mechanisms. Pharmacol Ther, 219: 107694. [PMID:32980443]

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