Anti-Human PD-L1 (CD274) (Durvalumab) (P690-GRP)

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 B7.1 4. 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 cells 5. In normal tissues, PD-L1/PD-1 ligation is crucial to maintaining homeostasis of the immune system and preventing autoimmunity during infection and inflammation 5. 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. Durvalumab was generated using IgG2 and IgG4 XenoMouse animals immunized with human PD-L1-Ig or CHO cells expressing human PD-L1 6. Hybridomas were screened for binding to human PD-L1-transfected HEK 293 cells and inhibition of PD-1 binding to PD-L1 expressing CHO cells. To avoid triggering antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity, the constant domain was then exchanged for a human IgG1 triple-mutant domain that reduces binding to C1q and Fc gamma receptors. Durvalumab binds specifically to PD-L1 and inhibits interaction with PD-1 and CD80. Durvalumab does not cross react with human PD-L2, B7-H3, or mouse PD-L1. Durvalumab has been investigated as an anti-tumor immunotherapeutic agent in various clinical trials and yields significant improvement in progression-free survival 7,8,9,10.