Anti-PD-1 [5C4.B8 (Nivolumab)]

Nivolumab binds to the extracellular portion of human PD-1 (2.6 nM - Scatchard analysis and SPR) - the antibody also binds to cynomolgus PD-1 with a similar affinity (3.9 nM - SPR). The antibody does not bind to other immunoglobulin superfamily proteins such as CD28, CTLA-4, ICOS and BTLA. The epitope of Nivolumab for both human and cynomolgus PD-1 includes the sequences SFVLNWYR-MSPSNQTDKLAAFPEDR (aa 29-53) and SGTYLCGAISLAPKAQIKE (aa 85-103), as shown by mass spectrometry of protease-treated fragments of PD-1 - these residues are thought to additionally be important for liand binding to PD-1. PD-1 is an inhibitory receptor expressed on the surface of T cells. It is able to bind to its ligands PDL-1 and PDL-2 which results in an inhibitory signal leading to decreased T cell proliferation, cytokine protuction and cytotoxic activtiy. PDL-1 is often expressed in human tumors such as melanoma, lung and kidney where it is able to overactivate PD-1 and plays a role in the evasion of cancer cells from the immune system.