Thursday, March 2, 2017

Immunotherapy

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Immunotherapy
Multiple Responses
1.
Immunotherapy is the "treatment of disease by inducing, enhancing, or suppressing an immune response". Immunotherapies designed to elicit or amplify an immune response are classified as activation immunotherapies, while immunotherapies that reduce or suppress are classified as suppression immunotherapies.

Immunomodulatory regimens often have fewer side effects than existing drugs, including less potential for creating resistance in microbial disease.

Cell-based immunotherapies are effective for some cancers. Immune effector cells such as lymphocytes, macrophages, dendritic cells, natural killer cells (NK Cell), cytotoxic T lymphocytes (CTL), etc., work together to defend the body against cancer by targeting abnormal antigens expressed on the surface of tumor cells.

Therapies such as granulocyte colony-stimulating factor (G-CSF), interferons, imiquimod and cellular membrane fractions from bacteria are licensed for medical use. Others including IL-2, IL-7, IL-12, various chemokines, synthetic cytosine phosphate-guanosine (CpG) oligodeoxynucleotides and glucans are involved in clinical and preclinical studies.

2.
What is cancer immunotherapy?
Immunotherapy is treatment that uses certain parts of a person’s immune system to fight diseases such as cancer. This can be done in a couple of ways:
  • Stimulating your own immune system to work harder or smarter to attack cancer cells
  • Giving you immune system components, such as man-made immune system proteins
Some types of immunotherapy are also sometimes called biologic therapy or biotherapy.

In the last few decades immunotherapy has become an important part of treating some types of cancer. Newer types of immune treatments are now being studied, and they’ll impact how we treat cancer in the future.

Immunotherapy includes treatments that work in different ways. Some boost the body’s immune system in a very general way. Others help train the immune system to attack cancer cells specifically.

Immunotherapy works better for some types of cancer than for others. It’s used by itself for some of these cancers, but for others it seems to work better when used with other types of treatment.

What the immune system does
Your immune system is a collection of organs, special cells, and substances that help protect you from infections and some other diseases. Immune cells and the substances they make travel through your body to protect it from germs that cause infections. They also help protect you from cancer in some ways.

The immune system keeps track of all of the substances normally found in the body. Any new substance that the immune system doesn’t recognize raises an alarm, causing the immune system to attack it. For example, germs contain substances such as certain proteins that are not normally found in the human body. The immune system sees these as “foreign” and attacks them. The immune response can destroy anything containing the foreign substance, such as germs or cancer cells.

The immune system has a tougher time targeting cancer cells, though. This is because cancer starts when cells become altered and start to grow out of control. The immune system doesn’t always recognize cancer cells as foreign.

Clearly there are limits on the immune system’s ability to fight cancer on its own, because many people with healthy immune systems still develop cancer. Sometimes the immune system doesn’t see the cancer cells as foreign because the cells aren’t different enough from normal cells. Sometimes the immune system recognizes the cancer cells, but the response might not be strong enough to destroy the cancer. Cancer cells themselves can also give off substances that keep the immune system in check.

To overcome this, researchers have found ways to help the immune system recognize cancer cells and strengthen its response so that it will destroy them.

Types of cancer immunotherapy
The main types of immunotherapy now being used to treat cancer include:
  • Monoclonal antibodies: These are man-made versions of immune system proteins. Antibodies can be very useful in treating cancer because they can be designed to attack a very specific part of a cancer cell.
  • Immune checkpoint inhibitors: These drugs basically take the ‘brakes’ off the immune system, which helps it recognize and attack cancer cells.
  • Cancer vaccines: Vaccines are substances put into the body to start an immune response against certain diseases. We usually think of them as being given to healthy people to help prevent infections. But some vaccines can help prevent or treat cancer.
  • Other, non-specific immunotherapies: These treatments boost the immune system in a general way, but this can still help the immune system attack cancer cells.

Immunotherapy drugs are now used to treat many different types of cancer. For more information about immunotherapy as a treatment for a specific cancer, please see our information on that type of cancer.

Many newer types of immunotherapy are now being studied for use against cancer. Some of these are discussed in “What’s new in cancer immunotherapy research?

3.
Understanding Immunotherapy
Approved by the Cancer.Net Editorial Board, 05/2016
Immunotherapy, also called biologic therapy, is a type of cancer treatment designed to boost the body's natural defenses to fight the cancer. It uses substances either made by the body or in a laboratory to improve or restore immune system function. Immunotherapy may work in the following ways:
  • Stopping or slowing the growth of cancer cells
  • Stopping cancer from spreading to other parts of the body
  • Helping the immune system work better at destroying cancer cells

There are several types of immunotherapy, including:
  • Monoclonal antibodies
  • Non-specific immunotherapies
  • Oncolytic virus therapy
  • T-cell therapy
  • Cancer vaccines

Monoclonal antibodies
When the body’s immune system detects something harmful, it produces antibodies. Antibodies are proteins that fight infection.

Monoclonal antibodies are a specific type of therapy made in a laboratory. They may be used in a variety of ways. For example, monoclonal antibodies can be used as a targeted therapy to block an abnormal protein in a cancer cell.

Monoclonal antibodies can also be used as an immunotherapy. For example, some monoclonal antibodies attach to specific proteins on cancer cells. This flags the cells for the body’s immune system so it can recognize and destroy those cells.

Other types of antibodies work by releasing the brakes on the immune system so it can destroy the cancer cells. Researchers have identified the PD-1/PD-L1  and CTLA-4 pathways as being critical to the immune system’s ability to control cancer growth. These pathways are often called “immune checkpoints.” Many  cancers use these pathways to evade the body’s immune system. Blocking these pathways with specific antibodies called immune checkpoint inhibitors allows the body’s immune system to respond to the cancer. Once the immune system is able to recognize and respond to the cancer, it can stop or slow cancer growth.

The following are examples of immune checkpoint inhibitors:
  • Ipilimumab (Yervoy)
  • Nivolumab (Opdivo)
  • Pembrolizumab (Keytruda).

Clinical trials of monoclonal antibodies are ongoing for several types of cancers. Learn about the latest immunotherapy research on the Cancer.Net Blog.   

The side effects of monoclonal antibody treatment depends on the purpose of the drug. For example, the side effects of monoclonal antibodies used for targeted therapy are different than those used for immunotherapy. The side effects of immune checkpoint inhibitors may include side effects similar to an allergic reaction.

Non-specific immunotherapies
Like monoclonal antibodies, non-specific immunotherapies also help the immune system destroy cancer cells. Most non-specific immunotherapies are given after or at the same time as another cancer treatment, such as chemotherapy or radiation therapy. However, some non-specific immunotherapies are given as the main cancer treatment.

Two common non-specific immunotherapies are:
  • Interferons. Interferons help the immune system fight cancer and may slow the growth of cancer cells. An interferon made in a laboratory, called interferon alpha (Roferon-A [2a], Intron A [2b], Alferon [2a]), is the most common type of   interferon used in cancer treatment. Side effects of interferon treatment may include flu-like symptoms, an increased risk of infection, rashes, and thinning hair.
  • Interleukins. Interleukins help the immune system produce cells that destroy  cancer. An interleukin made in a laboratory, called interleukin-2, IL-2, or aldesleukin (Proleukin), is used to treat kidney cancer and skin cancer, including melanoma. Common side effects of IL-2 treatment include weight gain and low blood pressure, which can be treated with other medications. Some people may also experience flu-like symptoms.

Oncolytic virus therapy
Oncolytic virus therapy is a new type of immunotherapy that uses genetically modified viruses to kill cancer cells. First, the doctor injects a virus into the tumor. The virus enters the cancer cells and makes copies of itself. As a result, the cells burst and die. As the cells die, they release specific substances called antigens. This triggers the patient’s immune system to target all the cancer cells in the body that have those same antigens. The virus does not enter healthy cells.

In October 2015, the U.S. Food and Drug Administration approved the first oncolytic virus therapy to treat melanoma. The virus used in the treatment is called talimogene laherparepvec (Imlygic), or T-VEC. The virus is a genetically modified version of the herpes simplex virus that causes cold sores. The doctor can inject T-VEC directly into areas of melanoma that a surgeon cannot remove. Patients receive a series of injections until there are no areas of melanoma left. Side effects can include:
  • Fatigue
  • Fever
  • Chills
  • Nausea
  • Flu-like symptoms
  • Pain at the injection site

Researchers are testing other oncolytic viruses for different types of cancer in clinical trials. They are also testing the viruses in combination with other treatments, such as chemotherapy.  

T-cell therapy
For this type of immunotherapy, some T cells are removed from a patient’s blood. Then, the cells are changed in a laboratory so they have specific proteins called receptors. These receptors allow those T cells to recognize the cancer cells. The changed T cells are grown in large numbers in the laboratory and returned to the patient’s body. Once there, they seek out and destroy cancer cells. This type of therapy is called chimeric antigen receptor (CAR) T-cell therapy.

Researchers are still studying this and other ways of modifying T cells to treat cancer. Currently, these treatments are only available in clinical trials.

Cancer vaccines
A vaccine is another method used to help the body fight disease. A vaccine exposes the immune system to an antigen. This triggers the immune system to recognize and destroy that protein or related materials. There are 2 types of cancer vaccines: prevention vaccines and treatment vaccines. Learn more about cancer vaccines.

Questions to ask the doctor
Talk with your doctor about whether immunotherapy may be part of your treatment plan. If so, consider asking the following 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 be a part of my treatment plan?
  • How will I receive immunotherapy treatment and how often?
  • What are the possible side effects of immunotherapy, both in the short term and the long term?
  • How will this treatment affect my daily life? Will I be able to work, exercise, and perform my usual activities?   
  • What immunotherapy clinical trials are available for me?    
  • Whom should I call for questions or problems?

4.
ImmunotherapyPrint
Immunotherapy is a type of cancer treatment that helps your immune system fight cancer. The immune system helps your body fight infections and other diseases. It is made up of white blood cells and organs and tissues of the lymph system.

Immunotherapy is a type of biological therapy. Biological therapy is a type of treatment that uses substances made from living organisms to treat cancer.

Types of Immunotherapy
Many different types of immunotherapy are used to treat cancer. They include:
  • Monoclonal antibodies, which are drugs that are designed to bind to specific targets in the body. They can cause an immune response that destroys cancer cells.
  • Other types of monoclonal antibodies can “mark” cancer cells so it is easier for the immune system to find and destroy them. These types of monoclonal antibodies may also be referred to as targeted therapy.
  • Adoptive cell transfer, which is a treatment that attempts to boost the natural ability of your T cells to fight cancer. T cells are a type of white blood cell and part of the immune system. Researchers take T cells from the tumor. They then isolate the T cells that are most active against your cancer or modify the genesin them to make them better able to find and destroy your cancer cells. Researchers then grow large batches of these T cells in the lab.
  • You may have treatments to reduce your immune cells. After these treatments, the T cells that were grown in the lab will be given back to you via a needle in your vein. The process of growing your T cells in the lab can take 2 to 8 weeks, depending on how fast they grow.
  • Cytokines, which are proteins that are made by your body’s cells. They play important roles in the body’s normal immune responses and also in the immune system’s ability to respond to cancer. The two main types of cytokines used to treat cancer are called interferons and interleukins.
  • Treatment Vaccines, which work against cancer by boosting your immune system’s response to cancer cells. Treatment vaccines are different from the ones that help prevent disease.
  • BCG, which stands for Bacillus Calmette-Guérin, is an immunotherapy that is used to treat bladder cancer. It is a weakened form of the bacteria that causes tuberculosis. 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.

Who Receives Immunotherapy
Immunotherapy is not yet as widely used as surgery, chemotherapy, and radiation therapy. However, immunotherapies have been approved to treat people with many types of cancer. To learn about immunotherapies that may be used to treat your cancer, see the PDQ® adult cancer treatment summaries and childhood cancer treatment summaries.

Many other immunotherapies are being studied in clinical trials, which are research studies involving people. To find a study that may be an option for you, visit Find a Clinical Trial.

How Immunotherapy Works against Cancer
One reason that cancer cells thrive is because they are able to hide from your immune system. Certain immunotherapies can mark cancer cells so it is easier for the immune system to find and destroy them. Other immunotherapies boost your immune system to work better against cancer.

Immunotherapy Can Cause Side Effects
Immunotherapy can cause side effects. The side effects you may have depend on the type of immunotherapy you receive and how your body reacts to it.

The most common side effects are skin reactions at the needle site. These side effects include:
  1. Pain
  2. Swelling
  3. Soreness
  4. Redness
  5. Itchiness
  6. Rash

You may have flu-like symptoms, which include:
  1. Chills
  2. Weakness
  3. Dizziness
  4. Muscle or joint aches
  5. Headache
  6. Trouble breathing
  7. Low or high blood pressure
  8. Other side effects might include:
  9. Swelling
  10. Weight gain from retaining fluid
  11. Heart palpitations
  12. Sinus congestion
  13. Risk of infection
  14. Immunotherapies may also cause severe or even fatal allergic reactions. However, these reactions are rare.

How Immunotherapy Is Given
Different forms of immunotherapy may be given in different ways. These include:
  • Intravenous (IV)
  • The immunotherapy goes directly into a vein.
  • Oral
  • The immunotherapy comes in pills or capsules that you swallow.
  • Topical
  • The immunotherapy comes in a cream that you rub onto your skin. This type of immunotherapy can be used for very early skin cancer.
  • Intravesical
  • The immunotherapy goes directly into the bladder.

Where You Go for Your Treatment
You may receive immunotherapy in a doctor’s office, clinic, or outpatient unit in a hospital. Outpatient means you do not spend the night in the hospital.

How Often You Will Receive Treatment
How often and how long you receive immunotherapy depends on:
  • Your type of cancer and how advanced it is
  • The type of immunotherapy you get
  • How your body reacts to treatment

You may have treatment every day, week, or month. Some immunotherapies are given in cycles. A cycle is a period of treatment followed by a period of rest. The rest period gives your body a chance to recover, respond to the immunotherapy, and build new healthy cells.

How Immunotherapy Makes You Feel
Immunotherapy affects people in different ways. How you feel depends on how healthy you are before treatment, your type of cancer, how advanced it is, the type of therapy you are getting, and the dose. Doctors and nurses cannot know for certain how you will feel during treatment.
How to Tell Whether Immunotherapy Is Working
You will see your doctor often. He or she will give you physical exams and ask you how you feel. You will have medical tests, such as blood tests and different types of scans. These tests will measure the size of your tumor and look for changes in your blood work.

5.
Is Immunotherapy Right For You?
Immunotherapy is one of the most exciting areas of new discoveries and treatments for many different kinds of cancer. Understanding how the immune system works is opening the doors to developing new treatments that are changing the way we think about and treat cancer.

Most people receiving immunotherapy are treated in specialized cancer centers and many of them are enrolled in clinical trials. This may change as more trials are completed and more drugs are approved by the Food and Drug Administration (FDA) to treat different kinds of cancer.

Your Immune System and Cancer
Your immune system is a network of cells, tissues and organs that works together to recognize and destroy foreign invaders such as bacteria and viruses or abnormal or unhealthy cells in your body

The most important function of the immune system is to know the difference between self and non-self. Self means your own body tissues. Non-self means any abnormal cell or foreign invader, such as bacteria, viruses, parasites and fungus. Normally, your immune system will not attack anything that it identifies as a healthy part of self.

The problem with cancer cells is that they arise from our cells, but there are differences. As they grow and spread, cancer cells undergo a series of changes, or mutations, becoming increasingly less like normal cells.

Sometimes our immune system can detect these differences and respond. Other times, the cancer cells slip through the defenses or are actually able to inhibit the immune system.

Researchers have known for many years that our immune systems do recognize and attack cancer cells.

But, the progress being made today in immunotherapy is the result of new understanding about the complex interaction between the immune system and cancer.

The goal of the field of immuno-oncology, also known as tumor immunology, is to understand exactly how the immune system interacts with the cancer, and then use that information to develop new immunotherapy treatments.

6.
Immunotherapy
Immunotherapy is a treatment that uses the body's own natural defenses to fight cancer. White blood cells (T cells) that make up the immune system can be stimulated in several ways by specially designed drugs that allow them to recognize and kill cancer cells.

Early immunotherapy drugs worked in a general way by boosting the body’s immune system to fight cancer cells. However, recent research has discovered several proteins on the surface of T cells that act like a brake, or checkpoint, preventing them from attacking cancer cells.

CTLA-4 is one such checkpoint. Research on CTLA-4 led scientist Jim Allison in 1996 to propose blocking the protein as a cancer therapy. The findings by Allison, now chairman of immunotherapy at MD Anderson, led to the development and approval of ipilimumab, an immune checkpoint inhibitor that turns off CTLA-4 and allows the T cells to do their work. Ipilimumab has extended survival in patients with advanced melanoma.

Another checkpoint is PD-1, discovered in 2000. Several drugs have been developed to turn off PD-1 in many types of cancer, allowing existing T cells near the tumor to attack.  Researchers continue to identify more checkpoints that can be exploited to fight cancer.

Other immunotherapies fall into two general categories.

Targeted immunotherapies attack specific proteins on the surface of cells that help identify cancer and stimulate an immune response. Common types include:

Monoclonal antibodies are designed to identify specific abnormalities on the surface of cancer cells. Monoclonal antibodies attach themselves to these abnormalities, marking them as a target for the immune system.

Cancer vaccines help the body recognize cancer cells and stimulate the immune system to destroy them. Some vaccines contain cancer cells harvested from the patient’s tumor. Others contain proteins designed to attach themselves to cancer cells.

General immunotherapies are non-specific treatments that do not affect the cancer itself. They work on proteins called cytokines that send signals to stimulate the body’s immune system to fight cancer cells. Common types include:

Interleukins control the growth and activity of T cells. More than a dozen interleukins have been identified. Interleukin-2 (IL-2) is used to treat kidney cancers and melanomas that have spread to other regions of the body. Other interleukins are being studied as possible treatments for other types of cancer.

Interferons are a group of three proteins released by T cells in reaction to invading organisms. Interferons increase the immune system's reaction to cancer cells. Interferon alpha (IFN-alfa) is currently being used to treat melanoma, kidney cancer and certain types of leukemia and lymphoma.

Colony Stimulating Factors (CSF) strengthen the immune system by stimulating the production of white blood cells in the bone marrow. CSF therapies are used to help elevate low white blood cell counts after chemotherapy.

7.
What is immunotherapy?
Immunotherapy is a broad category of anti-cancer therapies that use the body’s immune system to fight cancer cells. These cells are different from normal cells, in that they do not die normally. Think of these rapidly-dividing cells like an out-of-control copy machine that won’t stop creating images. These abnormal cells frequently change, or “mutate,” to evade the immune system. Immunotherapy drugs are designed to alert the immune system about these mutated cells so it can locate and destroy them.

How does immunotherapy spark the immune system to help fight cancer?
The immune system is always on patrol, like a police force charged with ridding the body of foreign invaders, such as viruses, bacteria or fungi. Lymph nodes, which make up most of the immune system, serve as police stations throughout the body. White blood cells, such as “T cells,” fight infection and cancer. They are the police officers. When a foreign invader is detected, the entire immune system is alerted through chemical signals, just as a police station would radio police officers to alert them about a problem.

Cancer cells are not recognized as invaders because they are the body’s own cells, only they’ve mutated and changed so that once-healthy lung cells no longer behave like lung cells. The immune system doesn’t recognize this distinction, allowing these dangerous cells to grow, divide and spread throughout the body. One way cancerous cells stay hidden is through the PD-1 receptor, which tricks the body’s police force into thinking cancer cells are normal. Certain immunotherapy drugs work by blocking this evasive maneuver with a PD-1 inhibitor, which quiets the PD-1 receptor, allowing the cancer cells to be exposed as invaders, and triggering the immune system to send out an alert and launch a system-wide attack.

Experienced care team
With our team approach to care, our doctors and clinicians work together to come up with treatment options that meet your needs. Immunotherapy may be an option for you if you have breast, prostate, brain,kidney or spinal cancer, along with non-Hodgkin lymphoma, leukemia or melanoma. The treatment may work better for some cancers, so your doctor would monitor your progress closely and may pair immunotherapy with other treatments.

Personalized treatment approach
Patients and their caregivers are the ones who ultimately decide which treatment they want to pursue. Our clinicians are sensitive to your concerns and work to design treatment options that are appropriate for your needs and goals. We will provide you with the information you need to make an informed decision about immunotherapy.

Managing side effects
Immunotherapy can cause a variety of side effects, including fatigue, nausea, mouth sores, diarrhea, high blood pressure and fluid buildup, usually in the legs. Breast cancer patients, in particular, may experience fever, chills, pain, weakness, vomiting, headaches and rashes. The side effects of immunotherapy generally become less severe after the first treatment.

Throughout your treatment, your care team will provide integrative oncology services, including nutrition therapy, naturopathic medicine, pain management, oncology rehabilitation, mind-body medicine and spiritual support. These therapies can help reduce side effects and improve your overall quality of life during immunotherapy.

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