Programmed death 1 (PD-1) receptor protein is usually found on the surface of T-cells, and helps keep immune responses in check. When it is bound to programmed death ligand-1 (PD-L1), which is often expressed in some malignant tumours, the complex helps stop T-leukocytes from killing other cells, including cancer cells.⁷

Blocking PD-1 inhibits its influence on the T-cell meaning the T-cell can increase its response and destroy cancer cells. Blocking PD-L1 receptors also reactivates the immune response to tumour cells.^2,7,8

MABs targeting PD-1 include nivolumab, dostarlimab, pembrolizumab and cemiplimab. PD-L1 inhibitors include atezolizumab and avelumab. Durvalumab selectively binds to PD-L1 blocking its interaction with the PD-1 receptor and with CD80, thereby potentiating an immune response to tumour cells.²

Cancers that respond to PD-1 and PD-L1 inhibition include melanoma, renal cell carcinoma, non-small cell lung cancer, malignant pleural mesothelioma, colorectal cancer, urothelial carcinoma, squamous cell cancers, classical Hodgkin lymphoma, oesophageal carcinoma, breast cancer and endometrial cancer.

Another target to control T cell activity is cytotoxic T-lymphocyte antigen-4 (CTLA-4). Ipilimumab inhibits CTLA-4, blocking signals which inhibit T-cell activity. This has the effect of increasing the number of reactive T-effector cells which can then work together to attack tumour cells. Ipilimumab is indicated for several of the cancers that PD-1 and PD-L1 inhibitors are effective against.⁴