Immune Checkpoint PD‐1/PD‐L1: Is There Life Beyond Antibodies?

The PD‐1/PD‐L1 interaction has emerged as a significant target in cancer immunotherapy. Current medications include monoclonal antibodies, which have shown impressive clinical results in the treatment of several types of tumors. The cocrystal structure of human PD‐1 and PD‐L1 is expected to be a valuable starting point for the design of novel inhibitors, along with the recent crystal structures with monoclonal antibodies, small molecules, and macrocycles. Crystal clear: FDA‐approved monoclonal antibodies (mAbs) that target the PD‐1/PD‐L1 interaction have revolutionized the field of cancer immunotherapy. The recent increase in X‐ray crystallography data for antibodies, small molecules (SM), and macrocycles targeting PD‐1 or PD‐L1 provides valuable insight for the rational design of novel drugs to inhibit this protein–protein interaction.