Atezolizumab
[CAS# 1380723-44-3]

Identification

• Classification: API >> Antineoplastic agents
• Name: Atezolizumab
• Synonyms: Tecentriq
• CAS Registry Number: 1380723-44-3

Safety Data

• Hazard Symbols: GHS07 Warning
• Hazard Statements: H302-H315-H319
• Precautionary Statements: P501-P270-P264-P280-P302+P352-P337+P313-P305+P351+P338-P362+P364-P332+P313-P301+P312+P330

Discovory and Applicatios

Atezolizumab is a humanized monoclonal antibody designed to target and inhibit programmed death-ligand 1 (PD-L1), a protein involved in suppressing the immune system's ability to detect and destroy cancer cells. It belongs to the class of immune checkpoint inhibitors that have transformed the treatment landscape for several malignancies by enabling the immune system to recognize and attack tumor cells more effectively. The development of atezolizumab is part of the broader progress in immuno-oncology that seeks to enhance antitumor immunity by blocking inhibitory signaling pathways used by cancer cells to evade immune surveillance.

The identification of PD-L1 as a key regulator of immune tolerance in tumors marked a significant breakthrough in cancer immunology. PD-L1 is often upregulated on the surface of tumor cells and binds to the PD-1 receptor on T cells, leading to the inactivation of cytotoxic T lymphocytes. This mechanism allows cancer cells to escape immune destruction. Atezolizumab was engineered to selectively bind to PD-L1 and prevent its interaction with both PD-1 and B7.1 (CD80), thereby restoring T cell activity and promoting an immune-mediated attack on tumors.

Atezolizumab was developed through a process of antibody engineering that involved humanization and affinity optimization to ensure high specificity and reduced immunogenicity. The compound was subjected to extensive preclinical testing, demonstrating its ability to stimulate immune responses in vitro and to inhibit tumor growth in animal models. Following these results, atezolizumab entered clinical trials and was evaluated for safety and efficacy in a range of cancers.

The first major clinical success of atezolizumab came in the treatment of urothelial carcinoma, a type of bladder cancer with limited treatment options. It received accelerated approval for this indication after demonstrating a meaningful response rate and durable tumor regression in patients who had progressed on platinum-based chemotherapy. Subsequent studies confirmed its benefit in a subset of patients with high PD-L1 expression on tumor-infiltrating immune cells.

Atezolizumab has since been approved for additional indications, including non-small cell lung cancer (NSCLC), triple-negative breast cancer (TNBC), hepatocellular carcinoma, and small cell lung cancer. In NSCLC, atezolizumab showed improved survival outcomes, particularly when used in combination with chemotherapy. In TNBC, a notoriously aggressive and difficult-to-treat cancer, atezolizumab combined with nab-paclitaxel provided a new option for patients with PD-L1–positive tumors.

The therapeutic action of atezolizumab is associated with reactivation of tumor-specific T cells and an increase in immune cell infiltration into the tumor microenvironment. Its effects are not limited to tumor regression but also include prolonged disease stabilization and increased overall survival in responders. These outcomes have helped establish immune checkpoint blockade as a central component of modern oncology.

As with other immune checkpoint inhibitors, atezolizumab is associated with a distinct profile of immune-related adverse events. These effects stem from the systemic activation of the immune system and can include inflammation of the skin, gastrointestinal tract, liver, endocrine organs, and lungs. Effective management of these events requires early recognition and prompt immunosuppressive treatment when necessary.

The impact of atezolizumab extends beyond its approved indications. It continues to be investigated in clinical trials across a variety of cancers, both as monotherapy and in combination with other treatments such as targeted therapies, chemotherapy, and additional immunotherapies. These studies aim to broaden the patient population that can benefit from immune checkpoint inhibition and to overcome resistance mechanisms that limit treatment efficacy in some individuals.

Atezolizumab represents a significant advancement in the treatment of cancer by harnessing the power of the immune system. Its discovery and clinical success have contributed to a paradigm shift in oncology, offering new hope to patients with previously limited therapeutic options and paving the way for the development of next-generation immunotherapies.

References

2017. Atezolizumab versus docetaxel in patients with previously treated non-small-cell lung cancer (OAK): a phase 3, open-label, multicentre randomised controlled trial. Lancet, 389(10066).
DOI: 10.1016/s0140-6736(16)32517-x

2018. Atezolizumab for First-Line Treatment of Metastatic Nonsquamous NSCLC. The New England Journal of Medicine, 378(24).
DOI: 10.1056/nejmoa1716948

2020. The IUPHAR Guide to Immunopharmacology: connecting immunology and pharmacology. Immunology, 160(1).
DOI: 10.1111/imm.13175