Atezolizumab is an immunotherapy drug known as an immune checkpoint inhibitor. As a humanized monoclonal antibody, it is a lab-engineered molecule that functions as a substitute antibody. The drug is designed to interact with a protein called Programmed Death-Ligand 1 (PD-L1). This interaction disrupts the communication between cancer cells and the body’s immune system, which helps the body fight certain cancers.
The Role of PD-L1 in Cancer
The immune system uses checkpoints, which are molecules on immune cells that regulate an immune response. Cancer cells can exploit these checkpoints to avoid being attacked. Programmed Death-Ligand 1 (PD-L1) is a protein found on some normal cells and many cancer cells that helps prevent the immune system from attacking the body’s own tissues.
When PD-L1 on a cell’s surface connects with its partner receptor, Programmed Death-1 (PD-1), on an immune T-cell, it sends an “off” signal. Cancer cells exploit this by displaying high levels of PD-L1, creating a disguise to hide from the immune system. This binding suppresses the T-cell’s ability to recognize and attack the cancerous cells. This immune evasion is a challenge in cancer treatment, as it allows the tumor to grow and spread without being controlled by the body’s natural defenses.
How Atezolizumab Works
Atezolizumab is a monoclonal antibody engineered to target the PD-L1 protein. It functions by binding directly to PD-L1 on tumor cells and some immune cells. This action physically blocks PD-L1 from connecting with its PD-1 receptors on T-cells.
With this inhibitory signal blocked, T-cells are no longer suppressed and can recognize cancer cells as harmful. This “unmasking” restores the immune system’s natural ability to launch an attack. The reactivated T-cells can then infiltrate the tumor and destroy the cancer cells.
Atezolizumab also blocks PD-L1 from interacting with another receptor, B7.1 (CD80), further releasing the brakes on the anti-tumor immune response. By targeting the PD-L1 protein, the drug helps create an environment that is active and hostile toward the cancer.
Cancers Treated with Atezolizumab
Atezolizumab is approved to treat several cancers, often in advanced or metastatic stages. It is used for certain forms of non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). For these lung cancers, it may be indicated after the disease has progressed through platinum-based chemotherapy.
Another application is treating urothelial carcinoma, a type of bladder cancer. It is prescribed for patients with advanced or metastatic disease that has worsened after chemotherapy. The drug is also an approved treatment for hepatocellular carcinoma, the most common type of liver cancer.
Atezolizumab is also used for alveolar soft part sarcoma. While previously used for some triple-negative breast cancers (TNBC), this indication has been discontinued in certain regions. The drug may be used alone or in combination with other treatments like chemotherapy to improve effectiveness.
The Importance of PD-L1 Testing
Before starting treatment, doctors perform a diagnostic test on a tumor tissue sample from a biopsy. This test measures the amount of PD-L1 protein on cancer cells and tumor-infiltrating immune cells, which is called the PD-L1 expression level. The results help oncologists determine how likely a patient is to benefit from the therapy.
A high level of PD-L1 expression, or “PD-L1 positive,” indicates a higher probability that the cancer will respond to an immune checkpoint inhibitor. For some cancers, treatment with atezolizumab was indicated for patients whose tumors met a specific PD-L1 threshold. The FDA-approved VENTANA PD-L1 (SP142) Assay is one companion diagnostic used to identify these patients.
PD-L1 expression is a biomarker, not a perfect predictor of success. Some patients with low or negative PD-L1 levels may still respond to the treatment, while not all patients with high expression will benefit. Research continues to explore other biomarkers to help refine patient selection for these therapies.
Potential Side Effects of Atezolizumab
Because atezolizumab stimulates the immune system, its side effects differ from traditional chemotherapy. The drug can cause immune-related adverse events. These occur when the activated immune system mistakenly attacks healthy cells and organs while fighting cancer.
Common side effects of atezolizumab can include:
- Fatigue
- Decreased appetite
- Nausea
- Cough
- Diarrhea
- Skin reactions like a rash and itching
More severe side effects involve inflammation of healthy organs, such as:
- Pneumonitis (inflammation of the lungs)
- Colitis (inflammation of the colon)
- Hepatitis (inflammation of the liver)
- Endocrinopathies (problems with hormone-producing glands)
Patients should report any new or worsening symptoms to their healthcare team immediately. When used in combination with other cancer drugs, side effects like nerve damage, anemia, and low white blood cell counts can also occur.