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Immunotherapy for Cancer

What is immunotherapy?

Your immune system does more than simply fight colds and flu. Throughout your life, your natural defenses seek out and destroy anything that is not recognized as part of the "self" -- including all kinds of germs and cancer cells -- before they have a chance to cause disease. Your immune system manages to destroy most rogue cells before they form a full-fledged tumor, but some of them get by your defenses. If you already have cancer, your immune system will still be working hard to keep your disease in check, but it probably can't do the job on its own.

In recent years, more and more cancer patients have received treatments designed to give the immune system the upper hand against cancer. This approach -- called immunotherapy or biological therapy -- isn't as widely used as radiation or chemotherapy. For most types of cancer, immunotherapy hasn't been shown to be more effective than these standard treatments. And like the others, it can cause its own unpleasant side effects.

But immunotherapy can still be a powerful tool, either on its own or combined with chemotherapy or radiation. For certain patients -- including some in the advanced stages of skin cancer or kidney cancer -- immunotherapy can offer more than the conventional options, even the possibility of a complete cure. For others, it's an additional, less toxic method of controlling their disease or reducing side effects from other treatments. In the years to come, as scientists learn more about the immune system, immunotherapy promises to become even more common and more effective.

Is it safe? What does it involve?

Immunotherapy often involves adding more immune cells, immune signaling molecules, or other biochemicals to the body. Unlike chemotherapy, which affects all fast-growing cells, immune treatments target specific processes or types of cells and should have a low impact on healthy tissues. The side effects depend on the particular biological agent used. Some have very mild side effects, while others cause serious problems.

The delivery will also depend on the agent used as well as your treatment plan. Some immunotherapy treatments are in the form of pills or shots you can take at home, while others are delivered intravenously (IV) in the hospital or clinic. Immunotherapy may be administered a couple of times a day or as seldom as every month or two.

What are the different types of immunotherapy?

There are two major types of immunotherapy: Treatments that add new disease-fighting cells to your body (T cells) and treatments that add other elements to your own immune system (such as antibodies, cytokines, and others). Many immunotherapy agents are experimental or investigational and are only available by enrolling in clinical trials.

Here's a brief look at some common therapies:

T cells. T cells are a type of immune cell that can recognize and destroy problem cells, either indirectly (helper T cells) or directly (killer T cells, also called cytotoxic T lymphocytes or CTLs). In some cancer patients, there are CTLs that can recognize tumor cells.

T cell therapy is an approach that works by boosting this natural immune response -- taking these cells out, making more of them in the lab, and putting them back in the patient. Usually in combination with other therapies, T cell therapy can sometimes shrink tumors such as melanomas. Side effects can include fever and chills.

Monoclonal antibodies. The B cells in your immune system produce antibodies against bacteria, viruses, toxins, and other cells that they don't recognize as part of your own body. (Regular vaccines work by stimulating your immune cells to produce antibodies, so they are available in case they are needed in the future.)

In this form of immunotherapy, patients receive large intravenous doses of monoclonal antibodies, which are produced in the laboratory. The term monoclonal simply means that all of the cells are exact copies of one another and are derived from a single cell.

Each type of monoclonal antibody is designed to attack a specific target. For example, patients with certain types of lung cancer, colon cancer, and breast cancer can be treated with a monoclonal antibody product called bevacizumab (Avastin). An especially aggressive form of breast cancer, the HER2-positive form of the disease, often responds well to trastuzumab (Herceptin). Monoclonal antibodies can also be used to fight certain types of lymphomas and leukemias.

While generally well tolerated, monoclonal antibodies can stimulate flu-like symptoms, including fatigue, fever, chills, nausea, and vomiting.

Cytokines. Cytokines are chemical messengers between various parts of the immune system. Some of the cytokines being used for cancer treatment include:

  • Interleukins. Interleukins stimulate or regulate immune cells. Some patients with advanced kidney cancer or melanoma (a type of skin cancer) can be completely cured with high-dose interleukin-2 treatment alone, but most will need a combination of treatments.

    Interleukin-2 (IL-2) can cause severe side effects, and can only be given to people with normal heart and lung function. Due to its toxicity, IL-2 is rarely used anymore. In addition to flu-like symptoms, side effects include weight gain, confusion, and a drop in blood pressure.

  • Interferon-alpha. Interferons are produced in response to bacteria, viruses, and parasites. They also have cancer-fighting properties. Interferon-alpha can act directly on cancer cells to slow their growth or help them develop into normal cells. It has been approved for melanoma, certain types of leukemia, and Kaposi sarcoma, a cancer most often seen in HIV/AIDS patients. Studies suggest that interferon-alpha may also be effective in treating kidney cancer and non-Hodgkin lymphoma.

    Side effects of interferon-alpha can include rashes, loss of appetite, thinning hair, and, ironically, a reduction of infection-fighting white blood cells. If your white blood cells get too low, you might be at risk for infections. In September 2009, the Food and Drug Administration updated the labeling for alpha interferon products to include statements regarding possible risk of stroke, serious retinal detachment, peripheral neuropathy, and pulmonary hypertension.

Cancer vaccines. Although we commonly think of vaccines as preventive measures, they can also be used to fight an active disease. Scientists hope that injecting fragments of cells or specific cancer-related proteins can stimulate the immune system and be used to treat the disease. In April 2010, the FDA approved the first cancer treatment vaccine. This vaccine, sipuleucel-T (Provenge, manufactured by Dendreon), is approved for use in some men with metastatic prostate cancer.

Preventive vaccines are more common, and two vaccines now in use can prevent certain cancers. A vaccine called Gardasil prevents infection by certain human papillomaviruses (HPV) that can cause cervical cancer. A vaccine against hepatitis B can prevent some cases of liver cancer related to the virus.

Gene therapy. In this experimental field, researchers introduce genetic material (DNA or RNA) into cancer cells. Once inside, these genes produce molecules that might stop cancerous cells from multiplying. There are many ways to go about this -- in different experiments, scientists are trying to produce cytokines (to attract a greater immune response), enzymes (to activate drugs), "suicide genes" (to make cancer cells self-destruct), antisense sequences ("opposites" that bind with problem-causing DNA or RNA), or good copies of cancer control genes that have mutated.

Progress in gene therapy has been very slow because of the difficulty of delivering the genes into the cells safely and getting the genes to "turn on" and manufacture the products needed. Despite these obstacles, it has had some success. Cancer gene therapy has been relatively safe; side effects are usually limited to cold or flu-like symptoms.

How will my doctor decide if immunotherapy is right for me?

Not all patients -- or all cancers -- are good candidates for immunotherapy. At this time, the approach isn't used very often for patients with cancer of the prostate or ovaries. And if your cancer was caught at an early stage or is responding well to other treatments, immunotherapy may simply not be necessary.

In certain cases, however, immunotherapy does seem to be more effective when used for some smaller, earlier-stage cancers. If your doctor does recommend immunotherapy, you will be getting a cutting-edge treatment that could make a big difference.

References

American Cancer Society. What is immunotherapy? October 2010.

American Cancer Society. Types of immunotherapy. October 2010.

National Cancer Institute. Biological therapies for cancer. Questions and answers. 2006.

Weiner, L.M. Cancer immunotherapythe endgame begins. New England Journal of Medicine. June 19, 2008. 358(25): 2664-2665.

Finn, O.J. Cancer immunology. New England Journal of Medicine. June 19, 2008. 358(25): 2704-2715.

American Cancer Society. Nonspecific immunotherapies and adjuvants. October 2010.

American Cancer Society. Monoclonal antibodies. December 2010.

National Cancer Institute. NIH. Biological Therapy. 2004.

Questions and Answers on Avastin. U.S. Food and Drug Administration. February 26, 2004.

NobelPrize.org. http://nobelprize.org/educational_games/medicine/immunity/immune-detail.html

Mackensen, A. et al. Phase I Study of Adoptive T-Cell Therapy Using Antigen-Specific CD8+ T Cells for the Treatment of Patients With Metastatic Melanoma J Clin Oncol 24:5060-5069

June, Carl H. Adoptive T cell therapy for cancer in the clinic. J Clin Invest. 2007 June 1; 117(6): 14661476.

NCI: Access to Investigational Drugs Q& A.

NCI: Cancer Vaccine Factsheet. August 4, 2010.

NCI: Gene Therapy for Cancer Q& A. August 2006.

CDC Pink Book Principles of Immunity

Cross, Deanna and James Burmester. Gene Therapy for Cancer Treatment: Past, Present and Future. Clinical Medicine & Research Volume 4, Number 3 : 218 227.

FDA. New class safety labeling updates for alpha interferon products. September 4, 2009.

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