All About Immunotherapy

What is the immune system?

Every person has an immune system. It helps keep us safe from infections and other threats to our health. These threats can be viruses, toxins, allergens, and bacteria.

In most cases, your immune system does not see cancer as a threat to your body. Cancer starts in cells inside your body. Viruses, bacteria, allergens, and toxins come from outside the body.

Cancer cells are mutated (changed) versions of normal cells. The immune system doesn’t see them as threats, so an immune response does not happen. Some types of cancer can change how the immune system works. Experts have found that the immune system can fight certain diseases, like some cancers, with a little bit of help. This is called immunotherapy.

What is immunotherapy?

Immunotherapy uses your body’s own immune system to find and kill cancer cells. Immunotherapy may also be called biologic therapy. Immunotherapy treatments may be used to:

• Attack cancer cells directly.
• Stimulate (rev up) your immune system to attack the cancer.
• Prevent cancer from coming back after treatment (recurring).

Immunotherapy can also help rebuild or restore your immune system. This makes it easier for your immune system to kill cancer cells and to stop cancer from spreading to other parts of your body (metastasizing).

Immunotherapy can treat many types of cancer, like leukemia, lymphoma, breast cancer, prostate cancer, lung cancer, bladder cancer, and melanoma. Immunotherapy is being studied in clinical trials for almost all other types of cancer.

What are the different types of immunotherapy?

There are many kinds of immunotherapy that act in different ways to treat cancer:

• Monoclonal antibodies (mABs): Antibodies are created in a lab to target a specific antigen (protein). These medications target something found on the surface of the cancer cell. This “marks” that cell to be destroyed by the immune system. These medications may also work by blocking a “receptor” found on cells that is needed for growth. Examples of monoclonal antibodies are rituximab (Rituxan®), bevacizumab (Avastin®), trastuzumab (Herceptin®), and denosumab (Xgeva®, Prolia®).
• Cancer vaccines: Cancer vaccines are made of cells that have been changed in the lab to create an immune response in your body. There are a few kinds of cancer vaccines, but mostly they work to either prevent disease (example: the HPV vaccine) or to treat the cancer directly (tumor cell vaccines, antigen vaccines, dendritic cell vaccines, or vector-based vaccines).
• Cytokine therapies: Cytokines help immune cells to “talk” to each other, while also helping start an immune response. When cytokine therapy is used to fight cancer, it works to create an immune system response. Examples of cytokines are interferon, interleukin, and colony stimulating factors like sargramostim (Leukine®, GM-CSF).
• Adoptive T-cell transfer: This therapy tries to make the body's T-cells fight cancer. There are two types of this treatment:
  • T-cells are removed from your tumor. More of these cells are then made outside your body in a lab. They are then re-infused back into your body.
  • T-cells are removed from your tumor. These cells are then changed in the lab to add new receptors, called chimeric antigen receptors (CAR-T). These receptors target specific antigens in cancer cells, starting the immune response against the cancer. Examples of CAR-T treatments are tisagenlecleucel and axicabtagene ciloleucel.
• Donor lymphocyte therapy (DLI) : DLI is when lymphocytes (a type of white blood cell) are taken from a donor and infused back into a different person who has already had an allogenic bone marrow transplant from the same donor. The donor lymphocytes may help find targets for the immune system to attack. This can start a remission or can help stop a relapse (the cancer coming back) in patients who are at high risk for relapse after bone marrow transplant. DLI can also cause graft versus host disease (GVHD), a possibly serious side effect where the recipient’s body is attacked by the donor immune cells.
• Radioimmunotherapy: This is a combination of a monoclonal antibody and a radiation source. Radiation can be delivered directly to the specific tumor cells, but often in lower doses and over a longer period of time. An example is ibritumomab tiuxetan (Zevalin®).
• Virus Immunotherapy: Viruses are used to infect the cancer cells, which then starts an immune system response against the virus (and the virus-infected cancer cells). Some viruses being used to study this therapy are the polio virus and the herpes simplex virus. These methods are still being studied in clinical trials.
• Immune Checkpoint Inhibitors: These medications stop tumor cells from inactivating T cells. This lets the T cell (and the immune system) stay active to fight the tumor. Examples of immune checkpoint inhibitors are ipilimumab (Yervoy®), nivolumab (Opdivo®), and pembrolizumab (Keytruda®).

How is immunotherapy given?

Immunotherapy may be given:

• Into a vein (intravenously, IV).
• By mouth (oral, PO).
• By injection, either under the skin (subcutaneous, SubQ) or into a muscle (intramuscular, IM).
• Therapies may also be given directly into a body cavity to treat a specific site. For example, bladder cancer can be treated with a Bacillus Calmette-Guerin (BCG, TICE®, TheraCys®) given into the bladder.

Many immunotherapies are approved by the U.S. Food and Drug Administration (FDA) but many more are still being tested in clinical trials. Depending on the type and stage of cancer, you may be treated with immunotherapy alone, or you may receive immunotherapy with other therapies (such as chemotherapy, surgery, or radiation therapy).

What are the side effects of immunotherapy?

While many immunotherapy medications are made up of things that are already found in your body, side effects can happen because of the higher levels of these things. The most common side effects happen because of the "revving up" and stimulation of your immune system. They can be:

• Fever.
• Chills.
• Body aches (flu-like symptoms).
• Nausea/vomiting.
• Not feeling hungry.
• Fatigue.

You may also have an allergic-type reaction. Signs of an allergic reaction are:

• Low blood pressure.
• Having a hard time breathing.
• Rash or swelling at the injection site.

Let your care team know right away if you feel any of these symptoms during or after your treatment.

Each therapy may have side effects specific to the cells that are being affected by the therapy. Your healthcare team will review possible side effects of the therapy you are receiving. Immunotherapy is new, and we are still learning what long-term side effects there may be later. Read more about side effects of immunotherapy at OncoLink.org.

How will I know if immunotherapy is working for me?

Chemotherapy and radiation often show tumors get smaller rather quickly, which can be seen on CT, MRI, or Pet Scans. Changes in tumor marker levels in the blood can also be tracked.

Immunotherapy responses are not tracked in the same way. First, immunotherapy can take much more time to work as they make the immune system attack the tumor. The tumor may still be growing, even though therapy is being delivered. The speed of response depends on the type of immunotherapy given. Your healthcare team will track your cancer and side effects throughout the course of treatment. It may take weeks or even months to see a response from your immune system.

Resources for More Information

Cancer Immunotherapy, American Cancer Society

http://www.cancer.org/treatment/treatmentsandsideeffects/treatmenttypes/immunotherapy/immunotherapy-toc

Immunotherapy, Leukemia and Lymphoma Society

https://www.lls.org/treatment/types-of-treatment/immunotherapy

Understanding Cancer Immunotherapy, Society for Immunotherapy of Cancer (SITC)

http://www.sitcancer.org/resources/patient-information