Cancer treatment vaccines are a type of immunotherapy that treats cancer by strengthening the body’s natural defenses against the cancer. Unlike cancer prevention vaccines, cancer treatment vaccines are designed to be used in people who already have cancer—they work against cancer cells, not against something that causes cancer.

The idea behind treatment vaccines is that cancer cells contain substances, called tumor-associated antigens, that are not present in normal cells or, if present, are at lower levels. Treatment vaccines can help the immune system learn to recognize and react to these antigens and destroy cancer cells that contain them.

Cancer treatment vaccines may be made in three main ways.

1. They can be made from your own tumor cells. This means they are custom-made so that they cause an immune response against features that are unique to your cancer.
2. They may be made from tumor-associated antigens that are found on cancer cells of many people with a specific type of cancer. Such a vaccine can cause an immune response in any patient whose cancer produces that antigen. This type of vaccine is still experimental.
3. They may be made from your own dendritic cells, which are a type of immune cell. Dendritic cell vaccines stimulate your immune system to respond to an antigen on tumor cells. One dendritic cell vaccine has been approved, sipuleucel-T, which is used to treat some men with advanced prostate cancer.

A different type of cancer treatment, called oncolytic virus therapy, is sometimes described as a type of cancer treatment vaccine. It uses an oncolytic virus, which is a virus that infects and breaks down cancer cells but does not harm normal cells.

The first FDA-approved oncolytic virus therapy is talimogene laherparepvec (T-VEC, or Imlygic®). It is based on herpes simplex virus type 1. Although this virus can infect both cancer and normal cells, normal cells are able to kill the virus while cancer cells cannot.

T-VEC is injected directly into a tumor. As the virus makes more and more copies of itself, it causes cancer cells to burst and die. The dying cells release new viruses and other substances that can cause an immune response against cancer cells throughout the body.

Sipuleucel-T is used to treat people with prostate cancer:

• that has spread to other parts of the body
• who have few or no symptoms
• whose cancer does not respond to hormone treatment

T-VEC is used to treat some people with melanoma that returns after surgery and cannot be removed with more surgery.

Cancer treatment vaccines can cause side effects, which affect people in different ways. The side effects you may have and how they make you feel will depend on how healthy you are before treatment, your type of cancer, how advanced it is, the type of treatment vaccine you are getting, and the dose.

Doctors and nurses cannot know for sure when or if side effects will occur or how serious they will be. So, it is important to know which signs to look for and what to do if you start to have problems.

Cancer treatment vaccines can cause flu-like symptoms, which include:

• fever
• chills
• weakness
• dizziness
• nausea or vomiting
• muscle or joint aches
• fatigue
• headache
• trouble breathing
• low or high blood pressure

Learn more about flu-like symptoms caused by cancer treatment.

You may have a severe allergic reaction.

Sipuleucel-T can cause stroke.

T-VEC can cause tumor lysis syndrome. In this syndrome, the tumor cells die and break apart in the blood. This changes certain chemicals in the blood, which may cause damage to organs like the kidneys, heart, and liver.

Since T-VEC is made from herpesvirus it can sometimes cause a herpesvirus infection that can lead to:

• pain, burning, or tingling in a blister around the mouth, genitals, fingers, or ears
• eye pain, sensitivity, discharge from the eyes, and blurry vision
• weakness in the arms and legs
• extreme fatigue and drowsiness
• confusion

Monoclonal antibodies are immune system proteins that are created in the lab. Antibodies are produced naturally by your body and help the immune system recognize germs that cause disease, such as bacteria and viruses, and mark them for destruction. Like your body’s own antibodies, monoclonal antibodies recognize specific targets.

Many monoclonal antibodies are used to treat cancer. They are a type of targeted cancer therapy, which means they are designed to interact with specific targets. Learn more about targeted therapy.

Some monoclonal antibodies are also immunotherapy because they help turn the immune system against cancer. For example, some monoclonal antibodies mark cancer cells so that the immune system will better recognize and destroy them. An example is rituximab, which binds to a protein called CD20 on B cells and some types of cancer cells, causing the immune system to kill them. B cells are a type of white blood cell.

Other monoclonal antibodies bring T cells close to cancer cells, helping the immune cells kill the cancer cells. An example is blinatumomab (Blincyto®), which binds to both CD19, a protein found on the surface of leukemia cells, and CD3, a protein on the surface of T cells. This process helps the T cells get close enough to the leukemia cells to respond to and kill them.

Many monoclonal antibodies have been approved to treat a wide variety of cancers.

To learn about specific treatments for your cancer, see the PDQ® adult cancer treatment summaries and childhood cancer treatment summaries.

Monoclonal antibodies can cause side effects, which can differ from person to person. The ones you may have and how they make you feel will depend on many factors, such as how healthy you are before treatment, your type of cancer, how advanced it is, the type of monoclonal antibody you are receiving, and the dose.

Doctors and nurses cannot know for sure when or if side effects will occur or how serious they will be. So, it is important to know which signs to look for and what to do if you start to have problems.

Like most types of immunotherapy, monoclonal antibodies can cause skin reactions at the needle site and flu-like symptoms.

Needle site reactions include:

• pain
• swelling
• soreness
• redness
• itchiness
• rash

Learn more about skin changes caused by cancer treatment.

Flu-like symptoms include:

• chills
• fatigue
• fever
• muscle aches and pains
• nausea
• vomiting
• diarrhea

Learn more about flu-like symptoms caused by cancer treatment.

Monoclonal antibodies can also cause:

• mouth and skin sores that can lead to serious infections
• high blood pressure
• congestive heart failure
• heart attacks
• inflammatory lung disease

Monoclonal antibodies can cause mild to severe allergic reactions while you are receiving the drug. In rare cases, the reaction is severe enough to cause death.

Some monoclonal antibodies can also cause capillary leak syndrome. This syndrome causes fluid and proteins to leak out of tiny blood vessels and flow into surrounding tissues, resulting in dangerously low blood pressure. Capillary leak syndrome may lead to multiple organ failure and shock.

Cytokine release syndrome can sometimes occur with monoclonal antibodies, but it is often mild. Cytokines are immune substances that have many different functions in the body, and a sudden increase in their levels can cause:

• fever
• nausea
• headache
• rash
• rapid heartbeat
• low blood pressure
• trouble breathing

How Monoclonal Antibodies Treat Cancer

Types of immune system modulators include cytokines, BCG, and immunomodulatory drugs.

Cytokines are proteins made by white blood cells. They play important roles in your body’s normal immune responses and in the immune system’s ability to respond to cancer.

Cytokines that are sometimes used to treat cancer:

• Interferons (INFs). Researchers have found that one type of interferon, called INF-alfa, can enhance your immune response to cancer cells by causing certain white blood cells, such as natural killer cells and dendritic cells, to become active. INF-alfa may also slow the growth of cancer cells or promote their death.
• Interleukins (ILs). There are more than a dozen interleukins, including IL-2, which is also called T-cell growth factor. IL-2 boosts the number of white blood cells in the body, including killer T cells and natural killer cells. Increasing these cells can cause an immune response against cancer. IL-2 also helps B cells (another type of white blood cell) produce certain substances that can target cancer cells.

Cytokines that are sometimes used to reduce side effects from cancer treatment are called hematopoietic growth factors. They promote the growth of blood cells that are damaged by chemotherapy:

• Erythropoietin, which increases the production of red blood cells.
• IL-11, which increases the production of platelets.
• Granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF), which both increase the number of white blood cells. Boosting white blood cells reduces the risk of infections. G-CSF and GM-CSF can also enhance the immune system response against cancer by increasing the number of cancer-fighting T cells.

BCG is a weakened form of the bacteria that causes tuberculosis. It does not cause disease in humans. BCG is used to treat bladder cancer. When inserted directly into the bladder with a catheter, BCG causes an immune response against cancer cells. It is also being studied in other types of cancer. BCG stands for Bacillus Calmette-Guérin.

Immunomodulatory drugs (also called biological response modifiers) stimulate the immune system. They include

• thalidomide (Thalomid®)
• lenalidomide (Revlimid®)
• pomalidomide (Pomalyst®)
• imiquimod (Aldara®, Zyclara®)

Thalidomide, lenaliodomide, and pomalidomide cause cells to release IL-2. They also stop tumors from forming new blood vessels. Tumors need to form new blood vessels to grow beyond a certain size. These three drugs may also be called angiogenesis inhibitors.

Imiquimod is a cream that you rub on the skin. It causes cells to release cytokines.

Nonspecific Immune Stimulation

Most immune-modulating agents are used to treat advanced cancer. Some are used to help manage side effects.

Immune-modulating agents can cause side effects, which affect people in different ways. The side effects you may have and how they make you feel will depend on how healthy you are before treatment, your type of cancer, how advanced it is, the type of immune-modulating agent you are getting, and the dose.

Doctors and nurses cannot know for sure when or if side effects will occur or how serious they will be. So, it is important to know which signs to look for and what to do if you start to have problems.

Immune-modulating agents can cause flu-like symptoms, which include

• fever
• chills
• weakness
• dizziness
• nausea or vomiting
• muscle or joint aches
• fatigue
• headache

Learn more about flu-like symptoms caused by cancer treatment.

Cytokines can also cause many serious side effects

• trouble breathing
• low or high blood pressure
• severe allergic reactions
• lowered blood counts, which can raise the risk of infections and cause bleeding problems
• blood clots
• problems with mood, behavior, thinking, and memory
• skin problems, such as rash, burning at injection site, and ulcers
• organ damage

BCG can also cause urinary side effects.

Thalidomide, lenalidomide, and pomalidomide can cause

• blood clots
• nerve problems that lead to pain, numbness, tingling, swelling, or muscle weakness in different parts of the body
• birth defects, if used during pregnancy

Imiquimod can cause skin reactions.

T-cell transfer therapy is a type of immunotherapy that makes your own immune cells better able to attack cancer. There are two main types of T-cell transfer therapy: tumor-infiltrating lymphocytes (or TIL) therapy and CAR T-cell therapy. Both involve collecting your own immune cells, growing large numbers of these cells in the lab, and then giving the cells back to you through a needle in your vein. T-cell transfer therapy is also called adoptive cell therapy, adoptive immunotherapy, and immune cell therapy.

The process of growing your T cells in the lab can take 2 to 8 weeks. During this time, you may have treatment with chemotherapy and, maybe, radiation therapy to get rid of other immune cells. Reducing your immune cells helps the transferred T cells to be more effective. After these treatments, the T cells that were grown in the lab will be given back to you via a needle in your vein.

• TIL therapy uses T cells called tumor-infiltrating lymphocytes that are found in your tumor. Doctors test these lymphocytes in the lab to find out which ones best recognize your tumor cells. Then, these selected lymphocytes are treated with substances that make them grow to large numbers quickly.

  

  Research on CAR T-Cell Therapy Rapidly Advancing

  Researchers hope to expand use of these immunotherapies, while making them safer, more effective.

  The idea behind this approach is that the lymphocytes that are in or near the tumor have already shown the ability to recognize your tumor cells. But there may not be enough of them to kill the tumor or to overcome the signals that the tumor is releasing to suppress the immune system. Giving you large numbers of the lymphocytes that react best with the tumor can help to overcome these barriers.

• CAR T-cell therapy is similar to TIL therapy, but your T cells are changed in the lab so that they make a type of protein known as CAR before they are grown and given back to you. CAR stands for chimeric antigen receptor. CARs are designed to allow the T cells to attach to specific proteins on the surface of the cancer cells, improving their ability to attack the cancer cells.

A TIL therapy called lifileucel (Amtagvi) has been approved by the Food and Drug Administration (FDA) to treat melanoma. And it has produced promising findings in other cancers, such as cervical squamous cell carcinoma and cholangiocarcinoma. However, this treatment is still experimental for those cancers.

First Cancer TIL Therapy Gets FDA Approval for Advanced Melanoma

The new treatment, lifileucel, was originally developed by NCI researchers and is the first cell therapy approved for a solid tumor.

Six CAR T-cell therapies have been approved by the FDA for blood cancers.

• axicabtagene ciloleucel (Yescarta)
• brexucabtagene autoleucel (Tecartus)
• ciltacabtagene autoleucel (Carvykti)
• idecabtagene vicleucel (Abecma)
• lisocabtagene maraleucel (Breyanzi)
• tisagenlecleucel (Kymriah)

CAR T-cell therapy has also been studied for the treatment of solid tumors, including breast and brain cancers, but use in such cancers is still experimental.

T-cell transfer therapy can cause side effects, which people experience in different ways. The side effects you may have and how serious they are will depend on how healthy you are before treatment, your type of cancer, how advanced it is, the type of T-cell transfer therapy you are receiving, and the dose.

Doctors and nurses cannot know for sure when or if side effects will occur or how they will affect you. So, it is important to know which signs to look for and what to do if you start to have problems.

CAR T-cell therapy can cause a serious side effect known as cytokine release syndrome. This syndrome is caused when the transferred T cells, or other immune cells responding to the new T cells, release a large amount of cytokines into the blood.

Cytokines are immune substances that have many different functions in the body. A sudden increase in their levels can cause:

• fever
• nausea
• headache
• rash
• rapid heartbeat
• low blood pressure
• trouble breathing

Most people have a mild form of cytokine release syndrome. But in some people, it may be severe or life-threatening.

Also, although CAR T cells are designed to recognize proteins that are found only on cancer cells, they can also sometimes recognize normal cells. Depending on which normal cells are recognized, this can cause a range of side effects, including organ damage.

TIL therapy can cause capillary leak syndrome. This syndrome causes fluid and proteins to leak out of tiny blood vessels and flow into surrounding tissues, resulting in dangerously low blood pressure. Capillary leak syndrome may lead to multiple organ failure and shock.

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Immune checkpoints are a normal part of the immune system. Their role is to prevent an immune response from being so strong that it destroys healthy cells in the body.

Immune checkpoints engage when proteins on the surface of immune cells called T cells recognize and bind to partner proteins on other cells, such as some tumor cells. These proteins are called immune checkpoint proteins. When the checkpoint and partner proteins bind together, they send an “off” signal to the T cells. This can prevent the immune system from destroying the cancer.

Immunotherapy drugs called immune checkpoint inhibitors work by blocking checkpoint proteins from binding with their partner proteins. This prevents the “off” signal from being sent, allowing the T cells to kill cancer cells.

One such drug acts against a checkpoint protein called CTLA-4. Other immune checkpoint inhibitors act against a checkpoint protein called PD-1 or its partner protein PD-L1. Some tumors turn down the T cell response by producing lots of PD-L1.

Immune checkpoint inhibitors are approved to treat some people with a variety of

FDA Approves First Immunotherapy to Target LAG-3

Opdualag, a combination of relatlimab and nivolumab, is now an initial treatment option for advanced melanoma.

cancer types, including:

• breast cancer
• bladder cancer
• cervical cancer
• colon cancer
• head and neck cancer
• Hodgkin lymphoma
• liver cancer
• lung cancer
• renal cell cancer (a type of kidney cancer)
• skin cancer, including melanoma
• stomach cancer
• rectal cancer
• any solid tumor that is not able to repair errors in its DNA that occur when the DNA is copied

Immune checkpoint inhibitors can cause side effects that affect people in different ways. The side effects you may have and how they make you feel will depend on how healthy you are before treatment, your type of cancer, how advanced it is, the type of immune checkpoint inhibitor you are receiving, and the dose.

Doctors and nurses cannot know for sure when or if side effects will occur or how serious they will be. So, it is important to know which signs to look for and what to do if they occur.

Common side effects of immune checkpoint inhibitors include:

• rash
• diarrhea
• fatigue

Rarer side effects of immune checkpoint inhibitors can include widespread inflammation. Depending on the organ of your body that is affected, inflammation can lead to:

• changes in skin color, rash, and feeling itchy, caused by skin inflammation
• cough and chest pains, caused by inflammation in the lungs
• belly pain and diarrhea, caused by inflammation in the colon
• diabetes, caused by inflammation in the pancreas
• hepatitis (inflammation of the liver)
• hypophysitis (inflammation of the pituitary gland)
• myocarditis (inflammation of the heart muscle)
• nephritis (inflammation of the kidney) and impaired kidney function
• overactive or underactive thyroid
• nervous system problems such as muscle weakness, numbness, and trouble breathing

Learn more about organ inflammation and immunotherapy.

Immune Checkpoint Inhibitors