This page was reviewed under our medical and editorial policy by

Priya Vishnubhotla, MD, Chief, Medical Oncology, City of Hope Atlanta

This page was updated on August 16, 2023.

The immune system protects the body from foreign invaders—such as germs—and cell changes that may be harmful. The immune system has its own checks and balances to keep it from being overly aggressive or destroying healthy cells along with those that are harmful.

Proteins on the surface of immune cells called T-cells are part of the system of checks and balances. T-cells send signals to control the immune system’s response to threats. When turned on, T-cells may destroy cancer cells. However, sometimes T-cells bind with other cell proteins. When this happens, the T-cells are turned “off,” preventing the immune system from destroying cancer cells.

Anti-cancer or immunotherapy drugs called immune checkpoint inhibitors are designed to prevent T-cells from partnering with proteins that turn them off. One type of immunotherapy drug that works against these checkpoint proteins is called cytotoxic T lymphocyte antigen-4 (CTLA-4) inhibitors.

What is CTLA-4?

CTLA-4 is a type of protein found on T-cells. Normally, it helps keep the immune system’s response to foreign invaders or harmful cell changes in check. However, when CTLA-4 binds with other proteins, specifically B7-1 and B7-2, it blocks T-cells from doing their job of recognizing and attacking cancer cells.

CTLA-4 was the first immune checkpoint protein to be targeted for immunotherapy.

CTLA-4 inhibitors

Anti-CTLA-4 drugs are a type of immune checkpoint inhibitor drug that helps treat cancer. Given as an infusion, they prevent T-cells from binding with partner proteins that may prevent them from doing their job of attacking unhealthy cells.

The CTLA-4 inhibitor ipilimumab is used to block CTLA-4, allowing T-cells to destroy cancer cells. It’s also called MDX-010 and Yervoy®. Tremelimumab (Imjudo®) is another immunotherapy drug, or monoclonal antibody, that targets CTLA-4.

CTLA-4 inhibitors may be used alone or with other drugs to treat:

It’s also being studied as a treatment for other cancers.

CTLA-4 inhibitors are often given in combination with other immune checkpoint inhibitors, including PD-L1 or PD-1 inhibitors.

Anti-CTLA-4 treatment side effects

Although immunotherapy drugs, including those that target CTLA-4, have positive benefits, their use may also have adverse side effects. It’s important to identify these adverse side effects early so they may be treated without compromising the efficacy of immune checkpoint inhibition. It’s difficult to determine who will experience which side effects, if any, because every patient is different. Many times, side effects are mild.

Potential anti-CTLA-4 treatment side effects

The side effects patients may experience are listed below.

Rash and/or itchy skin: Rash is the most common side effect of anti-CTLA-4 medications. Typically, rashes appear on the torso and extremities.

Diarrhea: Patients being treated with CTLA-4-blocking antibodies are likely to experience diarrhea and sometimes abdominal pain. Often, the diarrhea doesn’t start right away, but more likely starts after weeks of treatment. There may be blood in the diarrhea.

Hepatitis: A less common adverse effect, hepatitis (inflammation of the liver) is seen in some patients undergoing treatment with anti-CTLA-4 treatments. Most patients experience the side effect after eight to 12 weeks of treatment. It may include fatigue, fever and jaundice.

Endocrinopathy: Effects on the hormone system in the body may cause nausea, headache and fatigue. The most common endocrinopathies are hypophysitis (pituitary inflammation) and hypothyroidism (underactive thyroid). Other more rare side effects may include primary adrenal insufficiency, type 1 diabetes, hypercalcemia and hypoparathyroidism.

Arthritis: Though rare, joint pain and inflammation are possible side effects.

Neuropathy: Headache and vertigo may occur as side effects of therapy, and more rarely, peripheral neuropathy or worsening of preexisting neurological conditions such as myasthenia gravis may occur.

Opportunistic infections: Because patients’ immune systems are suppressed, they may be at risk for unusual or opportunistic infections.

Organs that may be affected by anti-CTLA-4 treatment

Other organs may be affected with anti-CTLA-4 treatments, though this occurs less frequently. These organs may include those listed below.

Lungs: Some patients may experience inflammation in the lungs, such as pneumonitis, which may cause coughing, wheezing or chest pain.

Eyes: Some patients may experience inflammation of components of the eye, which may cause inflammation and red eye. Symptoms may include light sensitivity, pain, dry eyes and blurry vision.

Kidneys: Some patients develop reduced function of the kidneys that may be related to treatment.

Heart: Chest pain, shortness of breath, heart palpitations or swelling may affect in some patients, usually in the first few weeks of treatment.

Pancreas: Pancreatitis (inflammation of the pancreas) has been reported in a small number of patients treated with anti-CTLA-4 treatments.

Other anti-CTLA-4 treatment reactions

Other reactions to treatment may include those listed below.

Infusion reactions: Patients may experience infusion reactions, such as fever, chills, facial flushing, dizziness and wheezing.

Autoimmune reactions: Patients may experience autoimmune reactions. Because checkpoint inhibitor drugs remove safeguards on the body’s immune system, they may make patients more vulnerable to autoimmune illnesses, where the body attacks itself.

Patients should report any adverse or unusual side effects to their care team immediately.

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