Anti-PD-1 inhibitors

Anti-PD-1 drugs are the latest and most exciting drugs in the battle against Melanoma and will revolutionise treatment. Anti-PD-1 monoclonal antibody is directed against the negative immunoregulatory human cell surface receptor PD-1 (programmed death 1). Anti-PD-1 human monoclonal antibody binds to and blocks the activation of PD-1, an immunoglobulin super family transmembrane protein, by its ligands PD-L1 and PD-L2, resulting in the activation of T-cells and cell-mediated immune responses against tumour cells or pathogens. Activated PD-1 negatively regulates T-cell activation and function through the suppression of P13k/Akt pathway activation. Thereby specifically blocking PD-1, the bodies’ immune system can kill tumour cells, as they are not switched off.

The PD-1 inhibitors nivolumab and pembrolizumab are now FDA-approved and most recently, Australia was the first country to register pembrolizumab for untreated melanoma patients as well as for those patients who have previously received ipilimumab treatment. This important step reflects the latest phase III trial result which reports that pembrolizumab is superior to the alternative immunotherapy agent, ipilimumab in patients with melanoma who have not received previous treatment. A second phase III trial, reported at the same time, which compared the combination of nivolumab and ipilimumab to ipilimumab alone shows that the combination of immunotherapies is very promising; however, side-effects may be problematic and further information on the safety of this strategy is awaited. There is now a considerable body of trial data that suggests single-agent nivolumab or pembrolizumab is safe, and well-tolerated by patients.

Anti-PD-1 inhibitors