Understanding Immunotherapy

Approved by the Cancer.Net Editorial Board, 05/2020

Immunotherapy is a type of cancer treatment that boosts the body’s natural defenses to fight cancer. It uses substances made by the body or in a laboratory to improve how your immune system works to find and destroy cancer cells.

How does the immune system fight cancer?

Your immune system consists of a complex process your body uses to fight illness. This process involves your cells, organs, and proteins. Cancer can commonly get around many of the immune system’s natural defenses, allowing cancer cells to continue to grow.

Different types of immunotherapy work in different ways. Some immunotherapy treatments help the immune system stop or slow the growth of cancer cells. Others help the immune system destroy cancer cells or stop the cancer from spreading to other parts of the body. Immunotherapy treatments can be used alone or combined with other cancer treatments.

There are many types of immunotherapy. They include:

Monoclonal antibodies and tumor-agnostic treatments, such as checkpoint inhibitors
Oncolytic virus therapy
T-cell therapy
Cancer vaccines

What are monoclonal antibodies and tumor-agnostic treatments?

When your immune system detects something harmful, it makes antibodies. Antibodies are proteins that fight infection by attaching to antigens, which are molecules that start the immune response in your body.

Monoclonal antibodies are made in a laboratory to boost your body’s natural antibodies or act as antibodies themselves. Monoclonal antibodies can help fight cancer in different ways. For example, they can be used to block the activity of abnormal proteins in cancer cells. This is also known as a targeted therapy, or cancer treatment that targets a cancer’s specific genes, proteins, or the tissue environment that helps the tumor grow and survive.

Other types of monoclonal antibodies boost your immune system by inhibiting or stopping immune checkpoints. An immune checkpoint is normally used by the body to naturally stop the immune system’s response and prevent it from attacking healthy cells. Cancer cells can find ways to hide from the immune system by activating these checkpoints. Checkpoint inhibitors stop the ability of cancer cells to stop the immune system from activating, and in turn, amplify your body’s immune system to help destroy cancer cells. Common checkpoints that these inhibitors affect are the PD-1/PD-L1 and CTLA-4 pathways.

Examples of immune checkpoint inhibitors are:

Ipilimumab (Yervoy)
Nivolumab (Opdivo)
Pembrolizumab (Keytruda)
Atezolizumab (Tecentriq)
Avelumab (Bavencio)
Durvalumab (Imfinzi)

Many checkpoint inhibitors are approved by the U.S. Food and Drug Administration (FDA) for specific cancers. There are also some checkpoint inhibitors are used to treat tumors anywhere in the body by focusing on specific genetic changes. These are called “tumor-agnostic treatments.”

For example, FDA has approved the checkpoint inhibitor drug called pembrolizumab to treat metastatic tumors that have a specific molecular alteration called microsatellite instability-high (MSI-H) or DNA mismatch repair deficiency (dMMR). A similar immunotherapy drug called nivolumab has also been approved to treat adults and children with MSI-H or dMMR metastatic colorectal cancer that has not been stopped by chemotherapy. Learn more about tumor-agnostic treatments.

The side effects of monoclonal antibody treatment depend on the drug’s purpose. For example, the side effects of monoclonal antibodies used for targeted therapy are not like those used for immunotherapy. The side effects of immune checkpoint inhibitors may include side effects similar to an allergic reaction.

What are non-specific immunotherapies?

Non-specific immunotherapies also help your immune system destroy cancer cells. Most people get this type of therapy after or with other cancer treatments, such as chemotherapy or radiation therapy. Sometimes non-specific immunotherapies are the main cancer treatment.

2 common non-specific immunotherapies are:

Interferons. Interferons are proteins that are produced by your immune system to alert your body that there is a pathogen, typically a virus, in your body. Interferons can be made in a laboratory to help your immune system fight cancer. They may also slow the growth of cancer cells. The most common type of interferon used in cancer treatment is called interferon alpha (Roferon-A [2a], Intron A [2b], Alferon [2a]). Side effects of interferon treatment may include flu-like symptoms, an increased risk of infection, skin rashes, and hair thinning.

Interleukins. Interleukins are proteins that help cells communicate and they can start an immune system response. The lab-made interleukin-2 (IL-2) or aldesleukin (Proleukin) can treat kidney cancer and skin cancer, including melanoma. Common side effects of IL-2 treatment include weight gain and low blood pressure. Some people also experience flu-like symptoms.

What is oncolytic virus therapy?

Oncolytic virus therapy uses viruses that have been changed in a laboratory to destroy cancer cells. First, the doctor injects the genetically modified virus into the tumor. The virus then enters the cancer cells and makes a copy of itself. As a result, this causes the cancer cells to burst and die. As the cells die, they release proteins that trigger your immune system to target any cancer cells in your body that have the same proteins as the dead cancer cells. The virus does not enter healthy cells.

In 2015, the FDA approved the first oncolytic virus therapy to treat later stages of melanoma that cannot be treated with surgery. The virus in the treatment is known as talimogene laherparepvec (Imlygic), or T-VEC. The virus is a modified version of the herpes simplex virus, the virus that causes cold sores. The doctor can inject T-VEC into areas of melanoma until there are no more melanoma cancer cells left. Side effects of oncolytic virus therapy can include feeling tired, fever, chills, and nausea. Some people also have flu-like symptoms and pain at the injection site.

Clinical trials are testing other oncolytic viruses for different cancers. They are also testing how the viruses work with other treatments, such as chemotherapy.

What is T-cell therapy?

T cells are immune cells that fight infection. In T-cell therapy, the doctor removes T cells from your blood. Then, a laboratory adds specific proteins called receptors to the cells. The receptors allow those T cells to recognize cancer cells. The changed T cells are put back into your body. Once there, they find and destroy cancer cells. This type of therapy is known as chimeric antigen receptor (CAR) T-cell therapy. Side effects include fevers, confusion, low blood pressure, and, in rare occasions, seizures.

CAR T-cell therapy works well in treating certain blood cancers. Researchers are still studying this and other ways of changing T cells to treat cancer.

What are cancer vaccines?

A cancer vaccine can also help your body fight disease. A vaccine exposes your immune system to a foreign protein, called an antigen. This triggers the immune system to recognize and destroy that antigen or related substances. There are 2 types of cancer vaccine: prevention vaccines and treatment vaccines.

In general, immunotherapy is an important approach to find new treatments for cancer. The examples above do not include every type of immunotherapy treatment. Researchers are studying many new drugs. You can learn more about immunotherapy in each cancer-specific section on Cancer.Net; Look at the "Types of Treatment" and "Latest Research" pages for specific information about immunotherapy for that type of cancer. You can also learn about the latest immunotherapy research on the Cancer.Net Blog.

Questions to ask your health care team

If immunotherapy is in your treatment plan, you may want to ask your health care team these questions:

What type of immunotherapy do you recommend? Why?
What are the goals of this treatment?
Will immunotherapy be my only treatment? If not, what other treatments will I need?
How will I receive immunotherapy treatment and how often?
What are the possible short-term and long-term side effects of immunotherapy?
What side effects I know about right away?
How will this treatment affect my daily life? Will I be able to work, exercise, and do my usual activities?
What immunotherapy clinical trials are open to me?
Whom should I call with questions or problems?