Approval Time : Aug. 16, 2018
Drug Type : Immunotherapy
Alteration : Positive Expression
Indications : Atezolizumab was approved for the treatment of patients with locally advanced or metastatic urothelial carcinoma who are not eligible for cisplatin-containing chemotherapy, and whose tumors express PD-L1 (PD-L1 stained tumor-infiltrating immune cells [IC] covering ≥5% of the tumor area) as determined by an FDA-approved test, or who are not eligible for any platinum-containing therapy regardless of level of tumor PD-L1 expression.
Mechanism Of Action :
PD-L1 may be expressed on tumor cells and/or tumor-infiltrating immune cells and can contribute to the inhibition of the anti-tumor immune response in the tumor microenvironment. Binding of PD-L1 to the PD-1 and B7.1 receptors found on T cells and antigen presenting cells suppresses cytotoxic T-cell activity, T-cell proliferation and cytokine production. Atezolizumab is a monoclonal antibody that binds to PD-L1 and blocks its interactions with both PD-1 and B7.1 receptors. This releases the PD-L1/PD-1 mediated inhibition of the immune response, including activation of the anti-tumor immune response without inducing antibody-dependent cellular cytotoxicity. In syngeneic mouse tumor models, blocking PD-L1 activity resulted in decreased tumor growth.
Dosage : The recommended dosage of atezolizumab is 1200 mg as an intravenous infusion over 60 minutes every 3 weeks until disease progression or unacceptable toxicity. If the first infusion is tolerated, all subsequent infusions may be delivered over 30 minutes.
Structure :
RSCB PDB
Title: Crystal structure of PD-L1 complexed with atezolizumab fab at 2.9A
Released: 2017-09-20
Method: X-RAY DIFFRACTION
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