Anti-PD-L1 Antibody (Atezolizumab)

Atezolizumab, also known as MPDL3280A, is an monoclonal IgG1 antibody targeting PD-L1 (Programmed death-ligand 1). The binding of Programmed Cell Death Protein 1 (PD-1), also known as CD279, a receptor expressed on activated T cells, to its ligands PD-L1 and PD-L2, negatively regulates immune responses. Interferon expression (particularly IFN-gamma) from activated T cells induces expression of PD-L1 on tumor cells, which serves as a mechanism of adaptive immune resistance in many cancers. The PD-1 ligands are found on most cancer cells, and the PD-1:PD-L1/2 interaction inhibits T cell activity and allows cancer cells to escape immune surveillance. The PD-1:PD-L1/2 pathway is also involved in regulating autoimmune responses, making these proteins promising therapeutic targets for autoimmune diseases such as multiple sclerosis (MS), psoriatic arthritis, lupus, and type I diabetes. The PD-1/PDL-1 pathway is targeted by immune checkpoint inhibitors approved for the treatment of cancer, such as Pembrolizumab (Keytruda(R)) and Nivolumab (Opdivo(R)), both of which are used for many types of cancer and were considered blockbuster drugs. Other anti-PD-1 antibodies approved for cancer treatment include Cemiplimab, Dostarlimab, Retifanlimab, Toripalimab, and Tislelizumab. PD-L1-directed checkpoint inhibitors approved for cancer treatment include Atezolizumab, Durvalumab, Avelumab, and Cosibelimab. Atezolizumab, sold under the name TECENTRIQ, is a monoclonal antibody targeting PD-L1 approved by the FDA for the treatment of several cancer types, such as NSCLC (non small cell lung cancer) and SCLC (small cell lung cancer). It is also being investigated as part of ADCs (antibody drug conjugates).