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Know Your Cancer

What is Immunotherapy in cancer

Immunotherapy is a type of treatment that uses the body's own immune system to recognize and kill cancer cells. Cancer cells often can fool the body into not recognizing they are dangerous. If the body can't tell the difference between cancer cells and healthy cells, cancer cells may be able to “hide” from the immune system. To identify cancer cells as a threat and target them for destruction, Immunotherapy uses substances either made by the body or in a laboratory to enhance recognition or effector function of the immune response against the cancer.

Different types of Immunotherapy exist. Each works in a unique way to slow and stop the growth of cancer cells, stop cancer cells from spreading to other parts of the body and help the immune system work better overall at destroying cancer cells. Some Immunotherapy treatments boost the body's immune system while others train the immune system to attack cancer cells

Checkpoint inhibitors are an important part of the immune system due to their ability to keep immune cells from attacking normal cells in the body. Checkpoints are proteins on immune cells that need to be turned on or off to start/stop an immune response. The immune system uses checkpoints to prevent itself from attacking normal cells in the body and deleted immune cells after their functions have been completed, for example following clearance of an infection. But melanoma cells sometimes hijack these checkpoints to avoid being attacked by the immune system. Checkpoint inhibitors target the checkpoint proteins, helping to restore the immune response against melanoma cells.

Cytokines are soluble molecules that enable immune cells to communicate with each other. Cytokines work together to make sure that the immune response is of the right strength and length of time. Laboratory-made versions of cytokines are sometimes used to boost the immune system in people with melanoma. Oncolytic viruses are viruses altered in a laboratory so that they preferentially infect and kill mainly cancer cells. Along with killing the cells directly, the viruses can also alert the immune system to attack the cancer cells. Cancer vaccines are substances that stimulate the immune system to fight infection or disease. Cancer vaccines strengthen the immune system against cancer cells.

Nonspecific immune stimulators boost the immune system in a general way to help the immune system attack cancer cells.

Certain immunotherapies work well when given alone. Others work better in combination with additional treatment strategies.

At present, the clinical use of Immunotherapy is largely restricted to the adjuvant treatment of Stage III and systemic treatment of Stage IV melanomas, although there is intense interest in evaluating Immunotherapy as neoadjuvant or adjuvant therapy for all stages.

Why is Immunotherapy needed?

Immunotherapy has the potential to achieve durable clinical responses in some patients. In addition, an improved quality of life may also make Immunotherapy an attractive choice for people who have this treatment option. Immunotherapy may be an option for patients to consider because the side effects, although prevalent, may be easier on patients compared to typical chemotherapy-related toxicities, and with appropriate attention, can be simple to manage. The side effect profile differs from other types of cancer therapeutics. Some side effects occur as a result of an overactive immune system, not the destruction of healthy cells, as often occurs with cytototoxic Chemotherapy. Because not as many healthy cells are damaged with immunotherapy, some patients have reported a different range of side effects.

One limitation to Immunotherapy is that it can be very effective in some patients but not in others. Researchers continue to explore why this happens to determine how to improve existing therapies and to develop new ones through clinical trials. Researchers are interested in identifying biomarkers that may be able to better predict which patients are likely to respond to which Immunotherapy agents or combinations.

Several Immunotherapy agents or regimens are currently approved by the FDA for the treatment of melanoma. Other novel treatments that are not yet FDA-approved may be accessible through clinical trials. Discuss the opportunity to participate in a clinical trial with your patients if they have not responded to other therapies or if you feel this may be the best treatment option for them. Provide them with multiple resources, and encourage them to become advocates for their own health by learning about and researching available clinical trials.

How is Immunotherapy given?

Different forms of Immunotherapy may be given in different ways.

These include:

How does Immunotherapy work against cancer?

As part of its normal function, the immune system detects and destroys abnormal cells and most likely prevents or curbs the growth of many cancers. For instance, immune cells are sometimes found in and around tumors. These cells, called tumor-infiltrating lymphocytes or TILs, are a sign that the immune system is responding to the tumor. People whose tumors contain TILs often do better than people whose tumors don't contain them.

Even though the immune system can prevent or slow cancer growth, cancer cells have ways to avoid destruction by the immune system. For example, cancer cells may:

  • Have genetic changes that make them less visible to the immune system.
  • Have proteins on their surface that turn off immune cells.
  • Change the normal cells around the tumor so they interfere with how the immune system responds to the cancer cells.

Immunotherapy helps the immune system to better act against cancer.

Side Effects of Immunotherapy

Immunotherapy can cause side effects, many of which happen when the immune system that has been revved-up to act against the cancer also acts against healthy cells and tissues in the body. Different people have different side effects. The ones you 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 Immunotherapy you are getting, and the dose.

You might be on Immunotherapy for a long time, and side effects can occur at any point during and after treatment. Doctors and nurses cannot know for certain when or if side effects will occur or how serious they will be. So, it is important to know what signs to look for and what to do if you start to have problems.

Some side effects are common with all types of Immunotherapy. For instance, you might have skin reactions at the needle site, which include:

  • Pain
  • Swelling
  • Soreness
  • Redness
  • Itchiness
  • Rash

You may have 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

Other side effects might include:

  • Swelling and weight gain from retaining fluid
  • Heart palpitations
  • Sinus congestion
  • Diarrhea
  • Risk of infection
  • Organ inflammation

Some types of Immunotherapy may cause severe or even fatal allergic and inflammation-related reactions. However, these reactions are rare.

What are the types of Immunotherapy?

Monoclonal antibodies (mABs)

Monoclonal antibodies are laboratory produced antibodies designed to recognise and bind to specific receptors found on the surface of cells. They are derived from natural antibodies, complex proteins derived from a single B cell made by the body's immunological defence system to recognise and fight foreign invaders such as bacteria and viruses.

How they work?

A MAB works by recognising and finding specific proteins on cells. Some work on cancer cells, others target proteins on cells of the immune system.

Each MAB recognises one particular protein. They work in different ways depending on the protein they are targeting. Trigger the immune system

Some MABs trigger the immune system to attack and kill cancer cells.

Although cancer cells are abnormal, they develop from normal cells so they can be difficult for the immune system to spot. Some MABs attach themselves to cancer cells, making it easier for the cells of the immune system to find them. This process is called antibody-dependent cell-mediated cytotoxicity or ADCC.

Examples of MABS that work in this way include:

  • rituximab (Mabthera) a treatment for chronic lymphocytic leukaemia (CLL) and some types of non Hodgkin lymphoma
  • cetuximab (Erbitux) a treatment for advanced bowel cancer and head and neck cancer
  • trastuzumab (Herceptin) used to treat Breast Cancer and stomach cancer

Help the immune system to attack cancer

Other MABs work by acting on cells of the immune system. For example, immunotherapies called checkpoint inhibitors block proteins that stop the immune system attacking cancer cells.

Checkpoint inhibitors block different proteins, including PD-1 and PD-L1 (programmed death ligand 1). So you might also hear some of these drugs called PD-1 inhibitors or PD-L1 inhibitors. Examples of checkpoint inhibitors include:

  • ipilimumab (Yervoy) a treatment for advanced melanoma
  • nivolumab (Opdivo)
  • pembrolizumab (Keytruda)

Nivolumab and pembrolizumab are used to treat different types of cancer, including Hodgkin Lymphoma and melanoma.

How you have them

You have MAB treatment as an injection under the skin (subcutaneous injection), or through a drip (infusion) into a vein. For some drugs, you have your first treatment into your vein, then further treatments as an injection under your skin.

How often you have treatment and how many treatments you need will depend on:

which MAB you have, the type of cancer you have

Testing

Before you have some types of MAB you might need to have tests using some of your cancer cells or a blood sample to find out whether the treatment is likely to work. These tests look for changes in certain proteins or genes.

You cancer specialist can tell you if this applies to your treatment. This is not the case for all MABs and you don't always need this test.

To test your cancer cells, your specialist needs a sample (biopsy) of your cancer. They might be able to test some tissue from a Biopsy or operation you have already had.

Side effects

All treatments have possible side effects. These can vary depending on the type of MAB you have.

Allergic reaction during treatment

A common side effect of some MABs is an allergic reaction to the drug. This reaction is most likely to happen during treatment and when you first have the treatment.

If this is possible with your drug, you might have paracetamol, a steroid and an antihistamine drug before treatment to prevent a reaction.

An allergic reaction can include these symptoms, though you may not have all of them:

  • breathlessness
  • fever and chills
  • an itchy rash
  • flushes and faintness

Your nurse will monitor you and treat any symptoms if they happen.

General side effects

Side effects might include:

  • skin changes such as red and sore skin or an itchy rash
  • diarrhoea
  • tiredness
  • flu-like symptoms such as chills, fever, dizziness
  • feeling or being sick

Cancer vaccines

Vaccines to treat cancer

Vaccines are a type of Immunotherapy. Research in this area is at an early stage and vaccines are mainly available as part of clinical trials.

What vaccines are?

Normally, vaccines help to protect us from disease. They are made from weakened or harmless versions of the disease they are being made to protect us from. This means that they don't cause the disease. When you have the vaccine, it stimulates the immune system into action. The immune system makes antibodies that can recognise and attack the harmless versions of the disease. Once the body has made these antibodies it can recognise the disease if you come into contact with it again. So you're protected from it.

Vaccines to treat cancer

Researchers are looking at vaccines as a possible treatment for cancer. In the same way that vaccines work against diseases, the vaccines are made to recognise proteins that are on particular cancer cells. This helps the immune system to recognise and mount an attack against those particular cancer cells. These vaccines might help to:

  • stop further growth of a cancer
  • prevent a cancer from coming back
  • destroy any cancer cells left behind after other treatments

Types

Scientists are studying many different types of cancer vaccines and how they work in different ways. More research is needed before they have a full picture of how well this type of treatment works and which cancers it may treat.

The following types of cancer vaccines are most commonly under investigation throughout the world:

Antigen vaccines

These vaccines are made from special proteins (antigens) in cancer cells. They aim to stimulate your immune system to attack the cancer. Scientists have worked out the genetic codes of many cancer cell proteins, so they can make them in the lab in large quantities.

Whole cell vaccines

A whole cell vaccine uses the whole cancer cell, not just a specific cell protein (antigen), to make the vaccine. Scientists make the vaccine from your own cancer cells, another person's cancer cells or cancer cells that were grown in the laboratory.

Dendritic cell vaccines

Dendritic cells help the immune system recognise and attack abnormal cells, such as cancer cells. To make the vaccine, scientists grow dendritic cells alongside cancer cells in the lab. The vaccine then stimulates your immune system to attack the cancer.

DNA vaccines

These vaccines are made with bits of DNA from cancer cells. They can be injected into the body to make the cells of the immune system better at responding to and destroying cancer cells.

Anti idiotype vaccines

This vaccine stimulates the body to make antibo dies against cancer cells.

Cytokine therapies

Cytokines are a group of proteins in the body that play an important part in boosting the immune system. Interferon and interleukin are types of cytokines found in the body. Scientists have developed man made versions of these to treat cancer.

The man made version of interleukin is called aldesleukin.

How interferon and aldesleukin work

Interferon and aldesleukin work in several ways, including:

  • interfering with the way cancer cells grow and multiply
  • stimulating the immune system and encouraging killer T cells and other cells to attack cancer cells
  • encouraging cancer cells to produce chemicals that attract immune system cells to them

Interferon

Interferon is also called interferon alfa or Intron A.

Doctors use interferon for several different types of cancer including:

  • kidney cancer (renal cell cancer)
  • melanoma
  • multiple myeloma
  • some types of leukaemia

You are more likely to have interferon as an injection just under the skin (subcutaneously). Or you might have it into the bloodstream through a drip (infusion). How often you have it depends on which type of cancer you are having treatment for. Most people have interferon 3 times a week. Or you might have it as a daily injection.

Aldesleukin

Aldesleukin is also called Interleukin 2, IL2 or Proleukin. In cancer care, doctors use it most often to treat kidney cancer. It is also in clinical trials for some other types of cancer. You are most likely to have it as an injection just under the skin (subcutaneously). But you may have it into a vein, either as an injection or through a drip. How often you have this drug depends on which cancer you are being treated for.

Side effects of interferon and aldesleukin

The side effects of interferon and aldesleukin include:

  • a drop in blood cells causing an increased risk of infection, bleeding problems, tiredness and breathlessness
  • flu-like symptoms
  • diarrhoea
  • tiredness and weakness (fatigue)
  • feeling sick
  • loss of appetite
  • Aldesleukin can also cause low blood pressure.

Adoptive T-cell transfer

CAR T-cell therapy

  • CAR T-cell therapy is a type of Immunotherapy. You might also hear it called a type of adoptive cell transfer.
  • CAR T-cell therapy is a very complex and specialist treatment. With this treatment, a specialist collects and makes a small change to your T cells. These then target the cancer cells.
  • It is available as a possible treatment for some children with leukaemia and some adults with Lymphoma. People with other types of cancer might have it as part of a clinical trial.

T cells

  • To understand CAR T-cell therapy more, it helps to understand what T cells do.
  • White blood cells called lymphocytes play an important part in fighting infection and diseases, including cancer. There are different types of lymphocytes. T cells are one type.
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  • T cells move around the body to find and destroy defective cells. When you come into contact with a new infection or disease, the body makes T cells to fight that specific infection or disease. It then keeps some in reserve so that if you come across the infection again your body can recognise it and attack it immediately.

CAR T-cell therapy

T cells are good at fighting infection. But it can be difficult for them to tell the difference between a cancer cell and a normal cell. So the cancer cells can hide away and not be recognised.

Scientists are trying to find ways to get T cells to recognise cancer cells. One possible way to do this might be CAR T-cell therapy.

What happens with this treatment, you have a sample of T cells taken from your blood. Your medical team do this through a process called apheresis.

First you have a tube put into a vein in each arm. One tube removes the blood and passes it into an apheresis machine. The machine separates the different parts of the blood. For CAR T-cell therapy, the machine takes out your T cells. The rest of your blood cells and normal blood fluid go back into your body through the tube in your other arm.

In the lab, they change the T cells. You might hear this called genetically engineering the T cell. The T cell is now a CAR T-cell. CAR stands for chimeric antigen receptor. These CAR T-cells are designed to recognise and target a specific protein on the cancer cells.

These changed T cells grow and multiply in the lab. Once there are enough cells you have a drip containing these cells back into your bloodstream. The aim is for the CAR T-cells to then recognise and attack the cancer cells.

The changes they make in the lab mean that they can stay in your body for long periods of time, recognising and attacking the specific cancer cells. Researchers are still looking into how long they might stay in the body.

There are different types of CAR T-cell therapy made by different companies. Examples include:

  • Tisagenlecleucel (Kymriah)
  • Axicabtagene ciloleucel (Yescarta)

Which cancer types?

CAR T-cell therapy is available for some children with leukaemia and some adults with Lymphoma. This followed decisions by the National Institute for Health and Care Excellence (NICE) in England in December 2018 and January 2019. And decisions by the Scottish Medicines Consortium (SMC) in 2019.

Side effects

This is a new treatment, so doctors might not know about all the possible side effects yet. Known side effects include:

  • cytokine-release syndrome
  • changes in the brain (neurological side effects)
  • no B cells or fewer B cells after treatment with CAR T-cells that target CD19

Cytokine release syndrome

Cytokines are group of proteins in the body that play an important part in boosting the immune system. CAR T-cell therapy stimulates the immune system to make large amounts of cytokines. It causes symptoms such as:

  • Fever (high temperature)
  • Dizziness due to low blood pressure
  • Difficulty breathing

This syndrome might happen in the first week of treatment. You can have treatment to reverse the syndrome.

Side effects affecting the brain (neurological side effects)

Sometimes CAR T-cells cause problems to the brain. Doctors call this neurotoxicity. Symptoms might include:

  • headaches
  • Altered consciousness
  • Becoming confused or disorientated
  • Speech changes
  • Seizures

The treating team monitors you, or your child, closely for any of these changes. The changes might go away on their own or you might need treatment, for example steroids. Treatment depends on the symptoms you, or your child, are experiencing and how serious they are.

What is radioimmunotherapy and how does it work?

Radioimmunotherapy (RIT) involves a small amount of radioactive material (radionuclide) — that is combined with a molecule engineered in a laboratory (monoclonal antibody). This monoclonal antibody-radionuclide compound is called a radiopharmaceutical. Monoclonal antibodies are able to recognize and bind to specific features of cells, such as antigens and cell receptors. When injected into the patient's bloodstream, the radiopharmaceutical attaches to cancer cells, delivering a high dose of radiation to be delivered to the tumor.

What conditions are treated with radioimmunotherapy?

There are two RIT agents approved by the U.S. Food and Drug Administration (FDA): Zevalin and Bexxar. Both of these are used to treat patients with B-cell Follicular non-Hodgkin Lymphoma (NHL) that has not responded to Chemotherapy treatment, although these can be used in some other types of lymphomas or scenarios as a part of the treatment for a patient's Lymphoma. Zevalin, consists of a radioactive molecule Yttrium-90 (Y-90) combined with the monoclonal antibody ibritumomab tiuxetan; Bexxar, is a compound consisting of Iodine-131 (I-131) and tositumomab. Currently, only Zevalin (Y-90 Ibritumomab tiuxetan) is available on the market.

What are the advantages of radioimmunotherapy?

RIT offers more personalized Cancer Treatment because radiopharmaceuticals can be tailored to the unique biologic characteristics of the patient‘s tumor, are highly selective in their ability to adhere to cancer cells, and can limit radiation exposure to healthy tissue.

As a result, RIT has fewer and less severe side effects and is generally well tolerated. Typical side effects are short-term and include fever, chills, reduced blood cell counts, low blood pressure, Diarrhea and rash. Occasionally, secondary side effects from low blood cell counts, such as infection or bleeding, can be more severe, although these are more rare, and usually managed even when they do occur. The two-week total treatment period for RIT is also much shorter than other cancer treatments, which can include daily Radiation therapy for six weeks and four to six courses of Chemotherapy administered over three or four weeks.

By contrast, Chemotherapy and Radiation therapy are non-targeted therapies that can kill both cancer cells and normal, healthy cells. These may be often accompanied by side effects including nausea, vomiting, hair loss, diminished white blood cell and Platelet counts, and a loss of energy. Although some of these symptoms are also present with RIT, they tend to be less severe.

Studies have shown that patients with resistant or refractory B-cell non-Hodgkin Lymphoma treated with RIT benefit from a prolonged remission.

Home care

The medical facility where the RIT treatment is performed will provide you with instructions for special care to be taken at home, including important steps to take immediately afterwards, and in the days and week following treatment. These instructions can vary between different facilities, and you should refer to the treating facility to give you more details.

Generally, one can return to work right after treatment, unless otherwise specified by the treating facility. There may be additional medications that may need to be adjusted or stopped temporarily prior to and after treatment, such as blood thinners, and this will be instructed by your medical provider.

Special Considerations:

The medical facility where the RIT treatment is performed will provide you with instructions for special care to be taken at home, including important steps to take immediately afterwards, and in the days and week following treatment. These instructions can vary between different facilities, and you should refer to the treating facility to give you more details.

Generally, one can return to work right after treatment, unless otherwise specified by the treating facility. There may be additional medications that may need to be adjusted or stopped temporarily prior to and after treatment, such as blood thinners, and this will be instructed by your medical provider.

Special Considerations

The medical facility where the RIT treatment is performed will provide you with instructions for special care to be taken at home, including important steps to take immediately afterwards, and in the days and week following treatment. These instructions can vary between different facilities, and you should refer to the treating facility to give you more details.

Generally, one can return to work right after treatment, unless otherwise specified by the treating facility. There may be additional medications that may need to be adjusted or stopped temporarily prior to and after treatment, such as blood thinners, and this will be instructed by your medical provider.