Anti-Human PD-L1 (CD274) (Avelumab) – Fc Muted™

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 cells6, 7.

Avelumab engages both adaptive and innate immune functions and mediates antibody-dependent cell-mediated cytotoxicity by retaining a native Fc region6, 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.