Immunotherapy 101

What is Immunotherapy?

  body defense

Photo Credit: The Cleveland Clinic

Immunotherapy is a treatment that utilizes the body’s own immune system to recognize and fight cancer.   It boosts the body’s natural defenses by either using substances made by the body or by using man-made components that make the immune system work better in attacking cancer.  Immunotherapy is also called biologic or biotherapy, since it uses substances made from living organisms to treat cancer.  Immunotherapy is not yet as widely used as surgery, chemotherapy and radiation therapy, but it has been approved to treat people with many types of cancer.  Clinical trials are ongoing to expand the use of immunotherapies for the treatment of many more kinds of cancer.  Currently, immunotherapies for mesothelioma are being researched and tested and are showing some promise.  However, they are not currently available for regular treatment.

 

How does Immunotherapy work?

The body’s immune system is designed to detect foreign invaders, such as bacteria or viruses, which could harm the body, and then target and destroy these invaders.  However, cancer cells typically avoid detection by the immune system because they evolve from the body’s normal cells.  This is because cancer cells are regular body cells that have mutated, or changed, to grow out of control.  Since they have some of the same protein markers as normal cells, the immune system does not recognize them as foreign invaders and leaves them alone, allowing the cancer to grow unchecked.  Immunotherapy is designed to alert the body’s immune system to the cancer cells so it will attack and destroy them.

Immunotherapy is a variety of treatments that work in different ways to improve or restore immune system function in fighting cancer, and can work in the following ways: 1) By stopping or slowing the growth of cancer cells, 2) By stopping cancer from spreading to other parts of the body, or 3) Helping the immune system work better at destroying cancer cells.  The specific types of immunotherapies used in cancer treatment are:

  • Monoclonal Antibodies
  • Adoptive T cell Transfer
  • Cytokines
  • Immune Checkpoint Inhibitors
  • Cancer Vaccines

Monoclonal Antibodies

Monoclonal antibodies are man-made versions of immune system proteins.  They are also known as “targeted therapies,” because these man-made antibodies target cancer cells, while leaving healthy cells unharmed.  Monoclonal antibodies mimic the immune system’s antibody response to pathogens in the body.  When the immune system detects a foreign substance in the body, it makes a large number of antibodies against the foreign invader.  The antibody is designed to stick to a protein on the invading substance called an antigen.  Once it finds the antigen on the foreign substance, it then alerts the immune system to attack the substance it has attached to.  Monoclonal antibodies are manufactured antibodies that are designed to stick to an antigen in a specific cancer. The manufactured antibodies are injected into patients and then attach themselves to a particular antigen on the cancer.  This then alerts the body’s immune system to find and attack the cancer cells.  The challenge for researchers has been in indentifying the specific antigen on a certain cancer.   So far, the FDA has approved monoclonal antibodies for use in the treatment of a dozen different cancers.

There are three different ways that monoclonal antibodies are used in the treatment of cancer:

  1. Naked Monoclonal Antibodies. These are monoclonal antibodies that work by themselves without a drug or radioactive material attached to them.  This is the most common way monoclonal antibodies are used.  They function by either attaching themselves onto cancer cell antigens and marking them for destruction by the immune system, or by blocking antigens on cancer cells that help them grow.
  2. Conjugated Monoclonal Antibodies. These are Monoclonal Antibodies that are joined to a chemotherapy drug or a radioactive particle.  The monoclonal antibody is used as a targeting mechanism, taking these substances directly to cancer cells, thereby lessening the damage to normal cells.  Conjugated monoclonal antibodies are also known as tagged, labeled or loaded antibodies.  They can be radiolabeled, meaning they have radioactive substances attached to them, or chemolabeled, meaning they have a chemotherapy drug attached to them.
  3. Bispecific Monoclonal Antibodies. These are two monoclonal antibodies that are joined together, which allows them to attach to two different antigens at the same time.  The purpose is for the monoclonal antibodies to bind to a cancer cell and an immune cell at the same time, thereby brining them together, and causing a more targeted immune response.

Monoclonal Antibodies are given intravenously (through a needle in the vein).  The side effects are similar to an allergic reaction and can include fever, chills, weakness, headache, nausea, vomiting, diarrhea, low blood pressure and rashes.  These side effects are typically the result of stimulating the immune system into an immune response.  They tend to be most common when first given, and can diminish over time.

 

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Adoptive T Cell Transfer

T cells are a type of white blood cell designed to hunt down and destroy foreign invaders within body.  Adoptive T Cell Transfer consists of taking T cells from a person’s cancerous tumor, isolating and/or modifying them, and then giving them back to the same person to fight their cancer.  After the T cells are removed from a tumor, they are then isolated to find out which ones are most active against the tumor or they are modified to make them more effective in destroying specific cancer cells.  Once they are identified or modified, the T cells are then grown in large batches, a process which can last from 2 to 8 weeks, depending on how fast a person’s T cells grow.  Once enough T cells are grown, they are injected back into the person.  Another name for this therapy is chimeric antigen receptor (CAR) T cell therapy.  Researchers are looking for other ways to use T cells in the treatment of cancer.

 

Cytokines

Cytokines are proteins made by immune system cells.  They play a vital role in regulating the communication and activity of the immune system and its ability to respond to cancer.  There are two groups of cytokines that are especially important in the treatment of cancer:

  1. These are a group of cytokines that help white blood cells communicate and grow more quickly to respond to a threat to the body.  There are more than a dozen kinds of interleukins, but one of them, Interleukin-2 (IL-2), has been shown to be especially helpful in the treatment of cancer.  IL-2 has been used both by itself to boost the immune system in response to cancer, or combined with chemotherapy drugs or other cytokines to boost its effect.  IL-2 can have very strong side effects, such as low blood pressure, abnormal heartbeat, chest pain and other heart problems, especially if combined with other treatments.   When IL-2 is administered in large doses, it requires a patient to be hospitalized.  Several other interleukins (IL-7, IL-12 and IL-21) are also being studied for use in cancer treatment.
  2. These are cytokines that help the body resist infections.  They are three proteins, released by T cells in reaction to foreign invaders in the body.  Interferons are named for the first three letters of the Greek alphabet:  interferon-alpha (IFN-alpha), interferon-beta (IFN-beta), and interferon-gamma (IFN-gamma).  Only IFN-alpha is used in the treatment of cancer.  It works by enhancing the ability of immune cells to attack cancer cells, and may also slow the growth of cancer cells or shrink the blood vessels that allow tumors to grow.  The side effects of IFN-alpha are flu-like symptoms, thinning hair, low white blood cell counts and skin rashes.

There are also drugs that have been developed that mimic cytokines in the body.  Three drugs that are currently in use are thalidomide (Thalomid), lenalidomide (Revlimid), and pmalidomide (Pomalyst).  These are known as immunomodulating drugs (IMiDs), and they work by enhancing the immune system’s response to cancer.  The side effects of these drugs include drowsiness, fatigue, low blood cell counts, and neuropathy (painful nerve damage).

 

Immune Checkpoint Inhibitors

The immune system has natural “brakes” or “checkpoints” that keep it from destroying healthy, normal cells.  Basically proteins on T cells, which are white blood cells that attack foreign invaders in the body, recognize and bind to a protein on a normal cell, telling the T cell not to attack it.  However, cancer cells, which are mutated normal body cells, can also use these checkpoints to avoid being detected by the immune system.  Immune Checkpoint Inhibitors are drugs that prevent the binding of T cell proteins to cancer cell proteins, allowing the immune system to be activated and attack the cancer.  There are two sets of proteins that are affected by Immune Checkpoint Inhibitors:

  1. PD-1 and PD-L1. PD-1 is a checkpoint on T cells that binds to PD-L1, which is a protein found on other cells.  When PD-1 and PD-L1 bind together, it communicates it works as an “off-switch” to the T cell, telling it to leave the other cell alone.  However, some cancer cells can have large amounts of PD-L1, causing them to escape being attacked by the immune system.  Immune Checkpoint Inhibitors, block either PD-1 or PD-L1, stopping the binding of T cells to cancer cells, then allowing the T cell to attack the cancer.  One of the main concerns with Immune Checkpoint Inhibitors is that they can also allow the immune system to attack normal, healthy cells in the body.  This can lead to serious side effects such as:  skin rash, fatigue, cough, nausea, loss of appetite and itching.  They can also cause organ damage, such as serious problems of in the lungs, intestines, liver, kidneys, hormone-making glands or other organs.
  2. CTLA-4. CTLA-4 is another protein that works to stop T cells from attacking other cells.  Like normal cells, cancerous cells can send signals to CTLA-4 receptors on T cells to prevent them from being attacked by the immune system.  Drugs that block the cancer cell’s ability to send signals to the CTLA-4 receptor then expose the cancer as an invader and allow the body’s immune system to respond.  An example of this is the drug, tremelimumab, which is being researched to help treat patients with mesothelioma.  Tremlimumab binds to the CTLA-4 receptor on the surface of T-cells, allowing T cells to recognize the cancer and potentially attack mesotheiloma cells.

 

Cancer Vaccines

Cancer vaccines come in two forms:  those that prevent cancer, and those that are used to treat cancer.  There are some forms of cancer that can be caused by viruses.  Cancer prevention vaccines work by preventing the virus that can cause the cancer.  In this way, they work the same as regular vaccines by exposing individuals to low-dose or killed viruses, which triggers an immune response.  Currently, cancer prevention vaccines are being used to prevent Human papillomavirus (HPV), which can lead to cervical cancer, anal cancer, vaginal, vulvar, penile and other cancers; and Hepatits B (HBV), which can lead to liver cancer.  Cancer prevention vaccines protect against cancer by targeting a virus that might lead to cancer, but they do not target the cancer cells directly.

Cancer treatment vaccines work by activating the immune system to target cancer cells in someone who has already developed cancer.  Cancer treatment vaccines can be made from cancer cells taken from patients, parts of cancer cells or even just the antigen on the cancer cell.  Vaccines are often combined with other substances, called adjuvants, to boost the immune system response further.   The vaccine introduces a special antigen from the cancer cell into the body, causing the immune system to respond by attacking the cancer cells.  The advantage of cancer treatment vaccines is that the immune system has memory for antigens to which it has been exposed, opening the possibility that the vaccine might work long after it is given. As of now, the most promising cancer treatment vaccine is Provenge, which is used in the treatment of prostate cancer.

About the Author

unnamed-5 Sri Ramakumar is a freelance writer with a Master of Science (MS) in Family Studies & Human Development and a Master of Social Work (MSW) from the University of Arizona and the University of Minnesota respectively.  She also has a Bachelor of Arts  in English Composition from the University of Washington.  She was also a research assistant at the University of Arizona studying the role of parenting in the social and emotional development of children. Currently, Ms. Ramakumar works as a freelance writer focusing on medical and behavioral health issues for various nonprofits. Ms. Ramakumar resides in Tucson, Arizona with her husband and four children.

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