A PD-L1 monoclonal antibody is a type of immunotherapy that leverages the body’s immune system to combat cancer. This treatment uses monoclonal antibodies, which are laboratory-created proteins engineered to attach to a specific target called Programmed Death-Ligand 1 (PD-L1). By binding to PD-L1, these antibodies help the immune system more effectively attack cancerous cells.
The Immune System Checkpoint Mechanism
The immune system has checks and balances, known as immune checkpoints, to prevent it from attacking healthy cells. One such checkpoint involves the interaction between Programmed Death-1 (PD-1) and Programmed Death-Ligand 1 (PD-L1). PD-1 is a receptor on activated immune cells, called T-cells, which are responsible for destroying threats like infections and abnormal cells.
Healthy cells have the PD-L1 protein on their surface. When a T-cell’s PD-1 receptor binds to the PD-L1 on these healthy cells, it sends an “off switch” signal to the T-cell. This signal tells the T-cell to leave the healthy cell alone, which is a normal part of maintaining immune balance and preventing autoimmune reactions.
Some cancer cells exploit this protective system by producing unusually high amounts of the PD-L1 protein on their surface. By displaying this high level of PD-L1, the cancer cells disguise themselves as healthy cells. When a T-cell encounters one of these cancer cells, its PD-1 receptor binds to the abundant PD-L1, deactivating the T-cell. This prevents it from launching an attack, allowing the tumor to evade the immune system and grow.
This process of immune evasion is a challenge in the body’s fight against cancer. The cancer cells use the PD-1/PD-L1 pathway as a shield, suppressing the immune response that should be eliminating them. This interaction leads to T-cell exhaustion and an inability to perform its function, contributing to tumor progression.
How PD-L1 Inhibitors Work
PD-L1 monoclonal antibodies are designed to counteract the defensive mechanism used by cancer cells. These antibodies bind to the PD-L1 protein on the surface of tumor cells. This action physically obstructs the PD-L1 protein, preventing it from interacting with the PD-1 receptor on T-cells. The antibody essentially covers the “off switch” that the cancer cell uses to deactivate the immune response.
By blocking this connection, the inhibitory signal is never sent to the T-cell. This releases the “brakes” on the immune cell, allowing it to recognize the cancer cell as a foreign threat and proceed with its natural function of destroying it. The reactivated T-cell can then mount an attack against the tumor. This process enables the patient’s own immune system to do the work.
This therapeutic strategy is a form of immune checkpoint inhibition. Several PD-L1 inhibitor drugs are used in clinical practice, including atezolizumab (Tecentriq), avelumab (Bavencio), and durvalumab (Imfinzi). These drugs are all monoclonal antibodies that share the same mechanism of blocking the PD-L1 protein to restore anti-tumor immunity.
The development of these inhibitors offers a different approach from traditional treatments like chemotherapy. Instead of using chemicals to destroy rapidly dividing cells, PD-L1 inhibitors harness the specificity and power of the immune system. This targeted action can lead to durable responses in some patients.
Cancers Treated with PD-L1 Inhibitors
PD-L1 inhibitors are approved for a growing list of cancers, often for patients with advanced or metastatic disease. Cancer types that can be treated with these drugs include:
- Non-small cell lung cancer (NSCLC)
- Urothelial carcinoma (a type of bladder cancer)
- Triple-negative breast cancer
- Gastric or gastroesophageal junction cancer
- Cervical cancer
- Merkel cell carcinoma
Before initiating therapy, a patient’s tumor tissue is often tested to measure the amount of PD-L1 protein present on the cancer cells. This is done through a laboratory technique called immunohistochemistry (IHC). The results of this test help determine the level of PD-L1 expression, which can inform treatment decisions.
The level of PD-L1 expression can sometimes predict how likely a patient is to respond to a PD-L1 inhibitor. A higher concentration of PD-L1 on tumor cells is associated with a greater likelihood of a positive response. For some cancers, regulatory bodies have approved these inhibitors for patients whose tumors express the protein above a certain threshold.
However, PD-L1 expression is not a perfect predictor. Some patients with low or even undetectable levels of PD-L1 may still benefit from these treatments, while not all patients with high levels will respond. Researchers continue to investigate additional biomarkers, like tumor mutational burden (TMB), to better identify which patients are most likely to benefit.
Administration and Potential Side Effects
PD-L1 monoclonal antibodies are administered to patients through an intravenous (IV) infusion. This procedure takes place in a clinical setting, such as a hospital or infusion center. The treatments are given at regular intervals, from every two to six weeks, depending on the drug and cancer being treated.
Because these drugs work by amplifying the immune system, their side effects are often immune-related. The immune system may begin to attack healthy tissues and organs in the body, causing inflammation. These are known as immune-related adverse events (irAEs) and can affect various parts of the body.
Common side effects can include skin issues like rash and itching. Inflammation of the colon, known as colitis, can cause diarrhea, while inflammation of the lungs, called pneumonitis, may lead to coughing and shortness of breath. Other potential side effects include hepatitis (inflammation of the liver) and issues with endocrine glands, such as the thyroid. Fatigue is also a common side effect.
While many of these side effects are mild to moderate, they can sometimes be serious. Patients should report any new or worsening symptoms to their healthcare team promptly. Early recognition and management of these immune-related adverse events are important to prevent them from becoming severe. Treatment for these side effects often involves corticosteroids to suppress the unwanted immune activity.