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 is a treatment that stimulates your body's immune system. It is used to help strengthen or restore the immune system’s ability to fight cancer.

The immune system defends our bodies against infection and disease.

Different cells and organs in the immune system do the following:

• look for unhealthy cells or something foreign to the body
• send messages to other cells in the body about an attack
• attack and destroy bacteria, viruses, fungi, parasites and other micro-organisms that cause infections
• attack and destroy abnormal cells, like cancer cells

When the immune system is defending the body against infection and disease, it's called the immune response.

Find out more about the immune system.

Cancer cells have gene mutations that turn the cell from a normal cell into a cancer cell. Although there are many different types of cancer, they all start because of cells that are growing abnormally and out of control. Cancer can start in any cell in the body.

The immune system knows these cancer cells shouldn’t be there and will attack them, but sometimes our immune system doesn’t notice them. In some cases, our immune system is not strong enough to destroy the cancer cells. Or cancer cells turn off our body’s immune response so that the cells in the immune system won’t see and attack them.

Immunotherapy works by boosting or strengthening our body’s immune response so that it can recognize and destroy cancer cells. It works better for some types of cancer, but not others – so not everyone with cancer will have immunotherapy.

Immunotherapy treatment is given as a drug. Immunotherapy drugs may be used by themselves or combined with treatments like chemotherapy or radiation therapy to work better against cancer.

You may be given immunotherapy to:

• stop or slow the growth of cancer
• stop the cancer from spreading to other parts of the body
• deliver toxins such as chemotherapy drugs or radiation directly to the cancer cells

Immunotherapy drugs used to treat cancer are prescribed by the medical oncologist on your healthcare team. When deciding which type of immunotherapy to offer, they will consider:

• the type of cancer, including any specific tumour markers or gene mutations found in the cancer cells
• the types of treatment you’ve already had
• your overall health, including any medical problems you have
• your lifestyle and what you prefer or want
• the potential side effects of the immunotherapy drug

Most immunotherapy drugs are given by needle into a vein (intravenously, or by IV) in a cancer treatment centre or hospital. The immunotherapy drug is usually given using a central venous catheter. It may also be injected directly into an organ (such as the bladder, for bladder cancer) or into the tumour itself (for melanoma skin cancer) .

Immunotherapy is sometimes given as a pill that you take by mouth (called oral immunotherapy) or a cream or ointment that you rub onto your skin (called topical immunotherapy).

Immunotherapy is given in a treatment cycle. The cycle will include certain days that you are given the drug, with several rest days in between. You may have immunotherapy on its own or with other treatments, such as chemotherapy and radiation therapy.

It's important to tell your healthcare team if you have an autoimmune disease. These are health conditions such as lupus, rheumatoid arthritis (RA), Crohn’s disease or multiple sclerosis (MS) that are caused by your immune system attacking your body instead of defending it. Having immunotherapy can make an autoimmune disease worse.

If you are having immunotherapy, your healthcare team will give you a letter and a card to carry with you. These will tell other healthcare professionals which immunotherapy drugs you are taking. They will also explain that you're at risk of developing certain side effects.

Immunotherapy drugs are grouped into different types, depending on how they work. Immunotherapy drugs can work in different ways to help the immune system recognize and destroy cancer cells. Some immunotherapy drugs can be grouped into more than one type because of the way they work with the immune system.

Monoclonal antibodies (mAbs) are made in the lab. Like the antibodies that your immune system makes, their job is to trigger an immune response. Some monoclonal antibodies work by finding a specific antigen (such as a protein) on a cancer cell and then attaching to it. Your immune system then knows to attack and destroy those cancer cells.

Monoclonal antibodies use proteins that are designed to act like human antibodies in the immune system. They can be made in 4 ways:

• Murine antibodies are made from mouse proteins. Drugs with murine antibodies end with the letters –omab.
• Human antibodies are made from artificial human proteins. Drugs with this type of antibody end with –umab.
• Humanized antibodies are made with parts of mouse proteins attached to human proteins. Humanized monoclonal antibody drugs end with –zumab.
• Chimeric antibodies also have mouse and human proteins attached, but they have more human than mouse proteins. Drugs with chimeric antibodies end with –imab.

All monoclonal antibodies stimulate the immune system to destroy cancer cells. But some types of monoclonal antibodies are also a targeted therapy because they target an abnormal protein in a cancer cell. They do this by:

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

There are different types of monoclonal antibodies. These include immune checkpoint inhibitors, conjugated monoclonal antibodies and bispecific antibodies.

The immune system normally uses proteins called checkpoints to stop T-cells from attacking healthy cells. These checkpoint proteins signal to the immune system to slow down or stop an immune response. Some cancer cells also have checkpoint proteins, which send signals to confuse the immune system and stop cancer cells from being attacked. The cancer can continue to grow as the cancer cells hide from the immune system.

Immune checkpoint inhibitors are a type of monoclonal antibody that blocks checkpoint proteins so that immune system cells can attack and kill the cancer cells. They are used to treat cancers such as non–small cell lung cancer, bladder cancer and kidney cancer.

The following are different checkpoint proteins that can be blocked by immune checkpoint inhibitors.

PD-1 is found on T-cells and stops them from attacking other cells in the body. Immune checkpoint inhibitors that target PD-1 boost the immune systemʼs response to attack cancer cells. Examples of PD-1 checkpoint inhibitors include:

• cemiplimab (Libtayo)
• nivolumab (Opdivo)
• pembrolizumab (Keytruda)

PD-L1 can be found on both normal cells and cancer cells. Some cancer cells have a lot of PD-L1, which helps protect them from being attacked by T cells. PD-L1 checkpoint inhibitors block the PD-L1 on cancer cells so that they can be attacked by T cells. Examples of PD-L1 checkpoint inhibitors include:

• atezolizumab (Tecentriq)
• avelumab (Bavencio)
• durvalumab (Imfinzi)

CTLA-4 is also found on T cells. It acts like a switch that turns off the immune system. CTLA-4 checkpoint inhibitors turn the switch back on so that the T cells can attack cancer cells. Examples of CTLA-4 checkpoint inhibitors include:

• ipilimumab (Yervoy)
• tremelimumab (Imjuno)

LAG-3 acts like an off-switch that stops T-cells from attacking other cells. LAG-3 checkpoint inhibitors boost the immune system by attaching to LAG-3 and blocking its off-switch from working. An example of a LAG-3 checkpoint inhibitor is relatlimab. It is combined with the PD-1 inhibitor nivolumab to make a drug called Opdualag, which is used to treat melanoma.

Conjugated monoclonal antibodies are drugs with a monoclonal antibody that is attached to a chemotherapy drug or a radioactive particle. Conjugated monoclonal antibodies are considered both an immunotherapy and a targeted therapy.

The following are different types of conjugated monoclonal antibodies.

An antibody drug conjugate (ADC) is a monoclonal antibody attached to a chemotherapy drug. The monoclonal antibody recognizes and attaches to the antigen on the cancer cells. The chemotherapy drug is then released into the cancer cell to destroy it.

Examples of ADCs include:

• brentuximab vedotin (Adcetris)
• mirvetuximab soravtansine (Elahere)
• polatuzumab vedotin (Polivy)
• sacituzumab govitecan (Trodelvy)
• trastuzumab deruxtecan (Enhertu)
• trastuzumab emtansine (Kadcyla or T-DM1)

A radiolabelled antibody conjugate is a monoclonal antibody attached to a radioactive particle. The monoclonal antibodies help find and bind to cancer cells, and then release the radiation to destroy them. Radiolabelled antibody conjugates may also be called radioimmunotherapy.

Ibritumomab (Zevalin) is an example of a radiolabelled antibody conjugate. It’s made up of a monoclonal antibody and the radioactive particle yttrium-90.

Bispecific antibodies are a type of immunotherapy designed to attach to 2 different targets –an immune cell and a cancer cell. Bispecific antibodies bring the 2 cells together to help the body's immune system attack the cancer cells.

Targeting 2 different antigens means that the bispecific antibody can boost the immune system in more than one way, making the drug more effective. But it also means that these drugs can have more side effects during treatment.

The 2 different proteins that are fused together in bispecific antigens are sometimes indicated in the drug name by -fusp.

Examples of bispecific antibody drugs include:

• amivantamab (Rybrevant)
• blinatumomab (Blincyto)
• tebentafusp (Kimmtrak)

CAR stands for chimeric antigen receptor. CAR T-cell therapy takes T cells from your body and changes them in a lab. The changed T cells are then returned to your body so they can find and attack cancer cells. CAR T-cell therapy can be an effective treatment for some cancers when other treatments have stopped working.

Before the T cells can be changed, your healthcare team will do a procedure called leukapheresis that removes white blood cells (including T cells) from your blood. Blood is removed from your body through an intravenous (IV) line, and the white blood cells are then separated from the rest of the blood using a special machine. The remaining blood is given back to you through another IV.

The T cells are then separated from other types of white blood cells. In the lab, the CAR is added to the T cells. This changes them into CAR T cells. Each type of cancer has a different antigen, so the CAR is made to recognize and attach to the antigen for that cancer. Over the next several weeks, more copies of your CAR T cells are grown in the lab. When there are enough CAR T cells, they’ll be given back to you through an IV. Once the CAR T cells attach to the cancer cells, they start to multiply and destroy more cancer cells.

Sometimes chemotherapy is given before starting CAR T-cell therapy. Giving a dose of chemotherapy can help the CAR T cells work better against the cancer. The chemotherapy can help lower the white blood cell counts, which allows more CAR T cells to multiply without being attacked by the immune system. The chemotherapy kills some cancer cells, allowing the CAR T cells to most effectively find and attack the remaining cancer cells.

Examples of CAR T-cell therapy drugs include:

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

Immunomodulating drugs boost the immune system, but we need more research to understand how they do this. Immunomodulating drugs include:

• lenalidomide (Revlimid)
• pomalidomide (Pomalyst)
• thalidomide (Thalomid)

Non-specific immunotherapy uses cytokines, growth factors and other substances to boost the immune system. Cytokines and growth factors are chemicals made in the body. But they can also be made in the lab and used as drugs to treat cancer.

Interleukin-2 (Proleukin) is made in a lab. It contains interleukin, which is a cytokine made by the body. 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 may be used to treat kidney cancer that has spread to other parts of the body.

Granulocyte colony stimulating factor (G-CSF) and granulocyte-macrophage colony stimulating factor (GM-CSF) are blood growth factors made in the lab 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 with other types of immunotherapy to boost the immune system. It is used with different types of cancer to lower the risk of infection and reduce the need for antibiotics.

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 and can detect cancer cells and other germs in the body. When the receptors detect cancer cells or germs, they signal to immune cells to attack them. Imiquimod (Aldara) is a toll-like receptor agonist that is sometimes used as a cream to treat early-stage basal cell carcinoma, a type of non-melanoma skin cancer.

Vaccines used to treat cancer are different from vaccines that are used to prevent diseases. Vaccines can also be used to treat cancer by boosting the immune response to attack cancer cells in the body. These are a type of therapeutic vaccine, which treat rather than prevent disease.

Oncolytic virus vaccines use viruses that have been changed in a lab so that they can find and destroy cancer cells. The vaccine releases copies of the virus into the body, which stimulates the immune system to recognize cancer cells. Once the oncolytic viruses get into the cancer cell, they infect or break down the cell by multiplying until the cell bursts.

Researchers are looking at vaccines as potential treatments for cancer. Health Canada has not yet approved any therapeutic vaccines to treat cancer.

Side effects of immunotherapy will depend mainly on the type of drug used, the dose given, how it’s given and your overall health. Side effects can happen with any type of treatment, though not everyone has them or experiences them in the same way. But some immunotherapy drugs can cause life-threatening side effects. And because immunotherapy is a new treatment, it’s possible that we don’t yet know all of the potential side effects.

If you develop side effects, they can happen at any time during, immediately after, a few days or even weeks after immunotherapy. Tell your healthcare team right away if you have side effects that you think might be from immunotherapy. The sooner you tell them, the sooner they can treat you for any problems, or suggest ways that you can manage them.

The following are some of the side effects of immunotherapy.

Flu-like symptoms are a common side effect of immunotherapy. You may have fever, chills, muscle and joint aches or pain, shortness of breath or a sore throat.

These symptoms often occur right after having immunotherapy, but they usually go away as you continue treatment and your body gets used to the drug.

Fatigue is a feeling of tiredness, exhaustion or a general lack of energy. Itʼs different from the tiredness a person usually feels at the end of the day and it can be a serious problem.

Fatigue is a common side effect caused by some types of immunotherapy. It’s often related to the dose of the drug given and usually occurs with flu-like symptoms.

Find out more about fatigue.

Skin problems are one of the most common side effects of immunotherapy. Immunotherapy drugs can cause itchy, painful skin rashes and changes in skin colour. Skin problems usually start a couple of months after you’ve started immunotherapy treatment. But they can occur at any time during treatment and even years after you have finished having immunotherapy.

If you have skin conditions like psoriasis or eczema before starting immunotherapy, your skin conditions can get worse once treatment begins.

Find out more about skin problems.

Diarrhea is the frequent passing of loose, watery stools (poop). Some immunotherapy drugs can cause severe diarrhea, which may start several weeks or months into treatment. People with inflammatory bowel disease or Crohn’s disease may have more problems with diarrhea when having immunotherapy.

Find out more about diarrhea.

Constipation is a condition in which stool is hard and dry and difficult to pass. The stool becomes hard and dry if it moves too slowly through the large intestine (bowel) or if the intestine takes too much water from it.

Some immunotherapy drugs can cause constipation.

Find out more about constipation.

An infusion reaction is a reaction to a drug given into a vein (intravenously, or by IV). It is sometimes an allergic reaction. An infusion reaction may happen when the drug is going into your vein or soon after.

If you have an infusion reaction to an immunotherapy drug, your healthcare team will give you medicines or stop your treatment to manage your reaction.

Find out more about negative drug reactions.

Cytokine release syndrome (CRS) is when immunotherapy causes the immune system to overreact. CRS is also called a cytokine storm or cytokine-associated toxicity. CAR T-cell therapy and bispecific antibodies can cause CRS.

CRS can cause mild to life-threatening symptoms. Symptoms of CRS will depend on which part of the body is most affected, but may include:

• fever and chills
• nausea and vomiting
• fatigue
• shortness of breath
• coughing
• diarrhea
• skin problems, especially a rash
• muscle and joint pain
• headaches
• low blood pressure
• changes in heart rate
• delirium

Treatment of CRS focuses on reducing inflammation in the body. Medicines such as corticosteroids or tocilizumab (Actemra, Tyenne) may be used. Other treatments may include:

• medicines to reduce fever
• oxygen or being put on a ventilator
• heart medicines
• intravenous (IV) fluids

Hemophagocytic lymphohistiocytosis and macrophage activation syndrome (HLH/MAS) are severe forms of cytokine release syndrome (CRS) in which white blood cells attack red blood cells. When this happens, the damaged red blood cells release too much ferritin, a protein that stores and controls the amount of iron in the blood. High levels of ferritin in the blood causes swelling, abnormal liver function and kidney failure. The high levels may also cause the lungs to fill with fluid (pulmonary edema), making it difficult to breathe.

HLH and MAS are treated like CRS, but most people with either syndrome will need care in an intensive care unit.

Monoclonal antibodies can cause low blood cell counts during treatment. They can also cause hypogammaglobulinemia, which is when your immune system has low levels of the antibody called immunoglobulin. If your immunglobulin levels are too low, you have a higher risk of developing infections.

Find out more about low blood cell counts.

Capillary leak syndrome is when the plasma part of the blood leaks out of the small blood vessels (capillaries) into the surrounding tissues, organs and spaces in the body. It’s a medical emergency that can cause a drop in blood pressure, organ failure, fluid in the lungs and heart problems. You will need to be treated in the hospital or cancer centre.

Symptoms of capillary leak syndrome include:

• swelling (edema) of the abdomen, arms and legs
• diarrhea
• nausea
• increased thirst
• headaches
• fatigue
• sudden weight gain
• feeling irritable

Treatment for capillary leak syndrome includes corticosteroids and IV fluids. Your healthcare team may also give you a type of medicine that reduces the amount of fluid in your body (called a diuretic).

Immunotherapy drugs can cause different types of heart problems, including:

• heart failure
• an irregular heartbeat
• coronary heart disease

Find out more about heart problems.

Immune effector cell-associated neurotoxicity syndrome (ICANS) can occur after treatment with CAR T-cell therapy or bispecific antibodies. This syndrome affects how the brain functions. Symptoms of ICANS include:

• headaches
• confusion
• disorientation
• problems concentrating
• speech problems
• loss of consciousness
• seizures
• muscle weakness

ICANS can range from very mild to life-threatening. Treatment includes corticosteroids, antiseizure medicines (anticonvulsants) and IV fluids. Other supportive care treatments may be given.

In rare cases, people who have had CAR T-cell therapy or bispecific antibodies develop a second cancer that isn’t related to the cancer being treated.

Find out more about second cancers.

The immunomodulating drugs thalidomide, lenalidomide and pomalidomide can harm a developing baby and cause severe birth defects if you are pregnant while taking them.

More research is needed to know whether other immunotherapy drugs can cause birth defects. Your healthcare team will recommend that you use birth control if it's possible for you to get pregnant or get someone pregnant while taking immunotherapy drugs. You will need to continue doing so for up to a year after you’ve finished treatment.

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