Anti-Human PD-L1 (Atezolizumab) (LT1750-GRP)

Atezolizumab is a humanized, monoclonal immunoglobulin-G1 antibody that binds to programmed death ligand 1 (PD-L1; CD274) and B7.1 (CD80)1. PD-L1 is a transmembrane protein, widely expressed in many types of tissues, that acts as a ligand for the immune inhibitory receptor protein programmed death 1 (PD-1)2,3,4. Interaction between PD-1 and PD-L1 triggers inhibitory signals that dampen T cell function. PD-1 is expressed on activated T cells and is overexpressed on many human cancer cell types and on various tumor-infiltrating immune cells. B7.1 is a transmembrane glycoprotein present on dendritic cells, activated B cells, and macrophages that induces T cell proliferation and cytokine production. When atezolizumab prevents binding of PD-L1 to B7.1, the T-cell-mediated immune response is further enhanced4. Atezolizumab was isolated by screening a human phage display library against a recombinant extracellular domain-Fc fusion of human PD-L11,5. A high-affinity antibody was selected from a single phage clone on a human IgG1 backbone. Because PD-L1 is expressed on activated T cells, the Fc region of atezolizumab was engineered to eliminate antibody-dependent cytotoxicity (ADCC) or complement-dependent cytotoxicity (CDC)1. An Asn to Ala change at position 298 was introduced in the CH2 domain of each heavy chain, rendering atezolizumab effectorless and incapable of binding to human Fcγ receptors1,5. Atezolizumab does not interfere with the interaction of PD-1 with ligand PD-L2 (CD273). Atezolizumab is used in cancer immunotherapy and has been approved for some patients by the FDA to treat hepatocellular carcinoma, melanoma, non-small cell lung cancer, small cell lung cancer, urothelial cancer, and triple negative breast cancer6.