All About Immunotherapy

Author: OncoLink Team
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What is the immune system? 

Each person has an immune system. It helps keep us safe from infections and other threats to the health of the body. These threats are viruses, toxins, allergens, and bacteria. 

In most cases, the immune system does not see cancer as a threat to the body. Cancer starts in cells within the 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 and 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.

What is immunotherapy?

Immunotherapy is a way of treating cancer that uses the 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) the immune system to respond to the disease. 
  • Prevent a cancer from coming back after treatment. 

Immunotherapy can also work to rebuild or restore the immune system. This makes it simpler for the immune system to kill cancer cells and to stop cancer from spreading to other parts of the body.

Immunotherapy medications 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.

Types of immunotherapy include: 

  • Monoclonal antibodies (mABs): Laboratory-created antibodies that target a specific antigen (protein). These medications work by targeting something found on the surface of the cancer cell, “marking” that cell to be destroyed by the immune system. These medications may also work by blocking a “receptor” found on cells that is important 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 direct an immune response. There are a few different types of cancer vaccines, but mostly they function either to 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 play a very specific role in the immune system. They allow different immune cells to “talk” to each other, while also helping in the start of an immune response. When cytokine therapy is used to fight cancer, it is focused on using the substances to start an immune system response. Examples of cytokines include interferoninterleukin, and colony stimulating factors such as 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:
    • The first removes T-cells directly from a patient’s tumor, makes many of these cells outside the body, and then re-infuses them back to the patient. 
    • The second method also removes T-cells from the patient, but the cells are then enhanced in the lab with new receptors, called chimeric antigen receptors (CAR-T). These receptors target specific antigens in the patient’s cancer cells, starting the immune response against the cancer. Examples of CAR-T treatments are tisagenlecleucel and axicabtagene ciloleucel.
  • Donor lymphocyte therapy (DLI):DLI involves the infusion of lymphocytes (type of white blood cell) from a donor to a patient who has already had an allogenic bone marrow transplant from the same donor. The donor lymphocytes may help in finding targets for the immune system to attack. This can induce remission or possible prevent 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 in which the recipient’s cells/tissues are attacked by the donor immune cells.
  • Radioimmunotherapy: This is a combination of a monoclonal antibody and a radiation source. This results in radiation being 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: This type of therapy uses viruses to infect the cancer cells, which then starts an immune system response against the virus (and the virus-infected cancer cells). Examples of 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 block tumor cells from inactivating T cells. This lets the T cell (and the immune system) remain active in fighting the tumor. Examples of immune checkpoint inhibitors include: ipilimumab (Yervoy®)nivolumab (Opdivo®) and pembrolizumab (Keytruda®).

How is immunotherapy given?

Immunotherapy medications may be given into a vein (intravenously, IV), by mouth (oral, PO), or 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, some patients may be treated with immunotherapy alone, while others may receive imunnotherapy with other therapies (i.e. chemotherapy, surgery, or radiation therapy).

What are the side effects of immunotherapy?

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

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

Patients 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 relatively new, and we are still learning what long-term side effects there may be later. 

How will I know if immunotherapy is working for me?

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

Immunotherapy responses are not measured in the same way. First, immunotherapy methods 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. In addition, 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, though 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

References

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Dougan, M., & Dranoff, G. (2012). Immunotherapy of cancer. In Innate Immune Regulation and Cancer Immunotherapy (pp. 391-414). Springer New York.

El-Jurdi, N., Reljic, T., Kumar, A., Pidala, J., Bazarbachi, A., Djulbegovic, B., & Kharfan-Dabaja, M. A. (2013). Efficacy of adoptive immunotherapy with donor lymphocyte infusion in relapsed lymphoid malignancies. Immunotherapy, 5(5), 457-466.

Haanen, J. B., & Robert, C. (2015). Immune checkpoint inhibitors. In Immuno-Oncology (Vol. 42, pp. 55-66). Karger Publishers.

Hinrichs, C. S., & Rosenberg, S. A. (2014). Exploiting the curative potential of adoptive T‐cell therapy for cancer. Immunological Reviews, 257(1), 56-71.

Kaufman, H. L., Kohlhapp, F. J., & Zloza, A. (2015). Oncolytic viruses: a new class of immunotherapy drugs. Nature Reviews Drug Discovery, 14(9), 642-662.

Lichty, B. D., Breitbach, C. J., Stojdl, D. F., & Bell, J. C. (2014). Going viral with cancer immunotherapy. Nature Reviews Cancer.

Pardoll, D. M. (2012). The blockade of immune checkpoints in cancer immunotherapy. Nature Reviews Cancer, 12(4), 252-264.

Restifo, N. P., Dudley, M. E., & Rosenberg, S. A. (2012). Adoptive immunotherapy for cancer: harnessing the T cell response. Nature Reviews Immunology, 12(4), 269-281.

Rosenberg, S. A., & Restifo, N. P. (2015). Adoptive cell transfer as personalized immunotherapy for human cancer. Science, 348(6230), 62-68.

Shuptrine, C. W., Surana, R., & Weiner, L. M. (2012, February). Monoclonal antibodies for the treatment of cancer. In Seminars in Cancer Biology (Vol. 22, No. 1, pp. 3-13). Academic Press.

Sim, G. C., & Radvanyi, L. (2014). The IL-2 cytokine family in cancer immunotherapy. Cytokine & Growth Factor Reviews, 25(4), 377-390.

Vacchelli, E., Aranda, F., Eggermont, A., Galon, J., Sautès-Fridman, C., Zitvogel, L., ... & Galluzzi, L. (2014). Trial Watch: Tumor-targeting monoclonal antibodies in cancer therapy. Oncoimmunology, 3(1), e27048.

West, H. J. (2015). Immune Checkpoint Inhibitors. JAMA Oncology, 1(1), 115-115.

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