Immunotherapy

Our immune system has the ability to find and destroy cancer cells. But cancer cells can sometimes hide from the immune system and avoid being destroyed. Cancer cells may also stop the immune system from working properly. Immunotherapy helps to strengthen or restore the immune system’s ability to fight cancer.

Immunotherapy is sometimes called biological therapy. You may also hear the term immuno-oncology, which is the study of how the immune system interacts with cancer cells in order to find ways to prevent or treat cancer.

The immune system defends and protects our bodies from infection and disease. It is made up of organs, special cells and substances that work together to find and fight germs such as viruses or bacteria or abnormal or unhealthy cells that cause disease such as cancer. Germs and cancer cells have molecules on their surface (called antigens) that trigger the immune system to find and destroy them. But some cancer cells can hide from the immune system because they look a lot like normal cells. In some cases, the immune system may find cancer cells, but it isn’t strong enough to destroy all of them. And some cancer cells can even change how the immune system responds so it doesn’t work properly.

Immunotherapy boosts the immune system or helps the immune system to find cancer and attack it. Immunotherapy is used to:

• stop or slow the growth of cancer
• stop cancer from spreading to other parts of the body
• help the immune system work better to destroy cancer cells
• deliver toxins, such as radiation or chemotherapy, directly to cancer cells

Learn more about the immune system.

Different types of immunotherapy are used to treat cancer.

Monoclonal antibodies are made in the lab. Like the antibodies that your immune system makes, their job is to trigger an immune system reaction. Some monoclonal antibodies work by finding a specific antigen (such as a protein) on a cancer cell and then attaching to it. The immune system then knows to attack and destroy those cells. One example of this type of monoclonal antibody is rituximab (Rituxan). Rituximab is used to treat some types of non-Hodgkin lymphoma and chronic lymphocytic leukemia (CLL).

Monoclonal antibodies are also a targeted therapy because they block or target an abnormal gene or protein in a cancer cell. They also work by:

• blocking growth signals and receptors that cause cancer to grow
• delivering radiation or chemotherapy to cancer cells

The immune system normally stops T cells (a type of immune system cell) from attacking normal cells in the body by using proteins called checkpoints. Checkpoints are part of a pathway that the immune system uses to slow down or put the brakes on an immune system response. Some cancer cells can send signals that confuse T cells by turning on a checkpoint pathway and stopping them from attacking cancer cells. This lets the cancer continue to grow because the cancer cells hide from the immune system.

Immune checkpoint inhibitors are monoclonal antibodies that work by blocking checkpoint proteins so that immune system cells can attack and kill the cancer cells. They are used to treat melanoma skin cancer, non–small cell lung cancer, kidney cancer and Hodgkin lymphoma.

There are 2 immune checkpoint pathways that can be blocked to allow the immune system to fight cancer. PD-1 is an immune checkpoint that stops T cells from attacking other cells in the body. It does this by attaching to PD-L1, a protein found on some normal and cancer cells. Some cancer cells have a lot of PD-L1, which helps protect them from being attacked by T cells. Monoclonal antibodies such as atezolizumab (Tecentriq), pembrolizumab (Keytruda) and nivolumab (Opdivo) target PD-1 or PD-L1 to help boost the immune system’s response to attack cancer cells and destroy them.

CTLA-4 is another immune checkpoint on T cells that the monoclonal antibody ipilimumab (Yervoy) can target. This helps boost the immune system’s response against cancer cells.

Monoclonal antibodies can be used to deliver radiation or chemotherapy. Monoclonal antibodies used to deliver radiation are attached to radioactive substances called radioactive isotopes. The antibodies help find and bind to cancer cells, and they then release the radiation to destroy the cancer cells.

When monoclonal antibodies are used to carry radioactive substances this treatment is also called radioimmunotherapy. Ibritumomab (Zevalin) is a type of radioimmunotherapy. It is made up of a monoclonal antibody and the radioactive isotope yttrium-90. It is used to treat some types of non-Hodgkin lymphoma.

Monoclonal antibodies are sometimes attached to chemotherapy drugs to make antibody drug conjugates. Brentuximab vedotin (Adcetris) is an antibody drug conjugate that targets a protein on the surface of cancer cells in people with Hodgkin lymphoma. Trastuzumab emtansine (Kadcyla or T-DM1) is another type of antibody drug conjugate that is sometimes used to treat women with HER2-positive metastatic breast cancer.

Non-specific immunotherapy uses cytokines, growth factors and other substances to give the immune system a boost to fight cancer. Cytokines are chemicals in the body that trigger the immune system to fight disease or germs that get into the body. But cytokines can also be made in the lab and used to treat cancer.

Interferon is a type of cytokine made by the body. Interferon that is made in a lab to treat cancer is called interferon alfa (Intron A, Wellferon). Interferon can help trigger a stronger immune response against cancer cells and may also slow the growth of cancer or cause cancer cells to die. Interferon alfa is used to treat melanoma and some types of blood cancers such as non-Hodgkin lymphoma and chronic myelogenous leukemia (CML).

Interleukin is another cytokine made by the body. Interleukin-2 (Proleukin) can be made in a lab. It helps the body to make more of certain types of immune cells that boost the immune system’s response. It also helps the body to make more antibodies against cancer cells. This helps the immune system to find cancer cells and destroy them. Interleukin-2 is sometimes used to treat kidney cancer and melanoma.

Granulocyte colony stimulating factor (G-CSF) and granulocyte-macrophage colony stimulating factor (GM-CSF) are blood growth factors that stimulate the bone marrow to make more granulocytes and macrophages, which are types of white blood cells that help fight infection. G-CSF and GM-CSF can also be given to boost the immune system along with other types of immunotherapy.

Bacillus Calmette-Guerin (BCG) is a type of bacteria that has been changed in the lab so it doesn’t cause disease. It causes inflammation in the bladder, which triggers an immune response to help attack and destroy cancer cells. BCG is used to treat early-stage bladder cancer.

Toll-like receptor agonists are drugs that bind to toll-like receptors and cause an immune response that kills cancer cells. Toll-like receptors are found on the surface of most immune cells that can detect cancer cells and other germs in the body. When the receptors detect cancer cells or germs, this signals immune cells to attack. Imiquimod (Aldara) is a toll-like receptor agonist that is sometimes used to treat early-stage basal cell carcinoma, a type of non-melanoma skin cancer.

Immunomodulating drugs boost the immune system, but we need more research to understand how they do this. Immunomodulating drugs include thalidomide (Thalomid), lenalidomide (Revlimid) and pomalidomide (Pomalyst). They are used to treat multiple myeloma and some other types of cancer.

You may have immunotherapy in different ways. It may be given as pills or capsules that are swallowed (orally), by needle into a vein (intravenously) or applied to the skin (topically).

Some immunotherapy drugs can only be given in the hospital. You can take others at home.

Immunotherapy is based on a set schedule, or protocol, that is based on your specific condition. Each course of treatment usually involves a treatment period followed by a recovery period.

You may have immunotherapy as a treatment on its own, but it is also used with other types of therapy, such as chemotherapy, radiation therapy or both.

Side effects can happen with any type of treatment. Most side effects of immunotherapy are mild and go away once the body gets used to the drug. If side effects are severe, your doctor may stop the therapy for a period of time or adjust the dose. Side effects of immunotherapy will depend mainly on the:

• type of drug, combination of drugs or combination of treatment
• dose
• how the drug is given (for example, by mouth or vein)
• your overall health

Everyone’s experience is different, but you may have these side effects with immunotherapy:

Flu-like symptoms are a common side effect of immunotherapy. You may have fever, chills, muscle and joint aches or pain, nausea, vomiting or loss of appetite (anorexia).

These symptoms often occur immediately after treatment. Giving the injection before bedtime and taking other medicines, such as acetaminophen (Tylenol), can help reduce these side effects. You may even be able to sleep through them.

Flu-like symptoms usually go away with continued therapy, once the body gets used to the drug. Check with your doctor or healthcare team if these symptoms do not go away or are bothersome.

Fatigue makes you feel more tired than usual and can interfere with daily activities and sleep. Fatigue is a common, temporary problem that can happen with some types of immunotherapy. It is often related to the dose of the drug given and usually goes along with flu-like symptoms.

Find out more about fatigue.

Some immunotherapy drugs can give you a rash and make your skin itchy. This can happen during treatment and may last after treatment. Tell the healthcare team if you experience these skin changes. They can suggest moisturizers and creams and may prescribe medicines to relieve the itchiness.

Some people also have a skin reaction where the needle is injected including swelling, redness, itchiness, rash and soreness.

The immunomodulating drugs thalidomide, lenalidomide and pomalidomide can cause severe birth defects if you are pregnant when you take them.

Be sure to report side effects to the healthcare team. Your team is there to help. Side effects can happen any time during, immediately after or a few days or weeks after immunotherapy. Sometimes late side effects develop months or years later. Most side effects go away on their own or can be treated, but some side effects may last a long time or become permanent.

For information on specific drugs, go to sources of drug information.