A CTLA-4 antibody is a type of cancer treatment known as an immune checkpoint inhibitor. It enhances the body’s immune system, enabling it to better identify and combat cancer cells. This therapy works by interfering with signals that cancer cells use to hide from the immune system. The treatment removes the “blinders” from immune cells, allowing them to see and attack the tumor, which empowers a patient’s own immune response.
How CTLA-4 Antibodies Unleash the Immune System
The immune system has powerful cells called T-cells, which find and destroy threats, including cancer cells. To prevent these T-cells from becoming overactive and harming healthy tissues, the body has natural “brakes” or checkpoints. One of these is a protein on T-cells called Cytotoxic T-Lymphocyte-Associated Protein 4, or CTLA-4. When CTLA-4 is activated, it tells the T-cell to power down as a normal balancing process.
Some cancer cells exploit this natural braking system to protect themselves from an immune attack. They can trigger the CTLA-4 checkpoint, effectively turning off the T-cells that should be targeting them. This allows the cancer to grow undetected by the body’s defenses.
This antibody works by binding to the CTLA-4 protein on T-cells. By blocking this “off-switch,” the antibody prevents cancer cells from deactivating the T-cells. This action “releases the brakes” on the immune response, keeping the T-cells in an active state to recognize and mount a sustained attack against tumor cells.
The therapeutic effect of CTLA-4 antibodies is also linked to their ability to reduce another type of T-cell, known as regulatory T-cells (Tregs), within the tumor. Tregs normally suppress immune activity, and by depleting them, the antibody further clears the way for cancer-fighting T-cells to work effectively. This dual action helps create a more effective anti-cancer immune response.
Cancers Treated with CTLA-4 Antibodies
The most prominent CTLA-4 antibody used in oncology is ipilimumab (Yervoy), and another is tremelimumab (Imjudo). These therapies are approved for treating several types of cancer and can produce long-term responses in some patients.
Initially approved for unresectable or metastatic melanoma, its application has expanded. It is frequently administered not as a standalone treatment but in combination with other immune checkpoint inhibitors, such as PD-1 or PD-L1 inhibitors. This combination approach often enhances the overall effectiveness. Approved uses include:
- Advanced renal cell carcinoma (the most common type of kidney cancer)
- Certain types of colorectal cancer
- Hepatocellular carcinoma (a form of liver cancer)
- Non-small cell lung cancer
- Malignant pleural mesothelioma
Understanding Immune-Related Side Effects
The mechanism that makes CTLA-4 antibodies effective against cancer can also cause a unique set of side effects. By stimulating the immune system, the treatment can lead to immune cells attacking healthy organs, a condition known as immune-related adverse events (irAEs). These side effects stem from an overactive immune response, unlike traditional chemotherapy.
These irAEs can affect various parts of the body. Skin-related issues are among the most common, presenting as rashes and itching. The gastrointestinal tract is also frequently affected, leading to symptoms like diarrhea and colitis, which is inflammation of the colon. In some cases, this inflammation can be severe.
Other organ systems can also be impacted. The liver may become inflamed, a condition called hepatitis, which is detected through routine blood tests. The endocrine system, which includes glands that produce hormones, can also be a target. This may lead to thyroid problems or hypophysitis, an inflammation of the pituitary gland. While many of these side effects are mild to moderate, they can become serious, so patients should report any new symptoms to their healthcare team promptly.
The Treatment Process and Management
Treatment with a CTLA-4 antibody is administered intravenously in a clinical setting, such as a hospital or an outpatient cancer center. The infusion itself lasts between 30 to 90 minutes. A standard course of treatment involves receiving the infusion every few weeks for a predetermined number of cycles.
If a patient develops immune-related side effects, the medical team has established protocols for managing them. The primary goal is to reduce the excessive immune activity without completely compromising the anti-cancer response. For mild to moderate side effects, management might involve topical creams for rashes or medications for diarrhea.
For more severe side effects, the main strategy is to suppress the overactive immune system using corticosteroid medications, such as prednisone. These drugs are powerful anti-inflammatories that can calm the immune response. In situations where side effects are severe, the medical team may decide to pause the CTLA-4 antibody treatment temporarily or stop it permanently. Close monitoring is part of the process to catch and manage these events early.