Anti-Human PD-L1 (CD274) (Avelumab) (IVMB0541)

Programmed cell death 1 ligand 1 (PD-L1; CD274; B7-H1) is a type I transmembrane glycoprotein widely expressed in many types of tissues that acts as a ligand for the immune inhibitory receptor programmed cell death 1 (PD-1; CD279)^{1, 2, 3} and B7.1⁴. The PD-1 pathway is responsible for T cell activation, proliferation, and cytotoxic secretion, with PD-1/PD-L1 interaction triggering inhibitory signals that dampen T cell function. PD-L1 also plays a critical role in the differentiation of inducible regulatory T cells⁵.

In normal tissues, PD-L1/PD-1 ligation is crucial to maintaining homeostasis of the immune system and preventing autoimmunity during infection and inflammation⁵. In the tumor microenvironment, their interaction provides an immune escape mechanism for tumor cells by turning off cytotoxic T cells. As such, blocking the PD-L1/PD-1 interaction is a target of many anti-cancer immunotherapies.

Avelumab is a human IgG1 lambda monoclonal antibody that blocks the interaction between PD-L1 and its receptors PD-1 and B7.1, thereby enabling T cell activation and restoration of the adaptive immune response⁴. Avelumab can lyse a range of human tumor cells in the presence of peripheral blood mononuclear cells or natural killer cells^{6, 7}. Avelumab engages both adaptive and innate immune functions and mediates antibody-dependent cell-mediated cytotoxicity by retaining a native Fc region^{6, 7}. Avelumab binds to a functional epitope comprising residues Y56, D61, E58, E60, Q66, R113 and M115 as well as a conformational epitope comprising residues 54-66 and 12-122 of human PD-L1⁸.