VivoGenie Anti-Human PD-L1 (CD274) (Durvalumab) (IVMB0402)

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.