What is immunotherapy?

Cancers treated: Breast cancer, lung cancer, melanoma, cervical cancer, leukemias, lymphomas, myelomas, prostate cancer, colorectal cancer, and ovarian cancer; others under investigation

Subclasses of this group:
Cytokines, including interferons, interleukins, and hematopoietic growth factors; monoclonal antibodies, which can be developed from mouse antibodies (murine), a combination of mouse and human antibodies (chimeric), human antibodies combined with a small amount of mouse antibody (humanized), or only human antibodies (human), antibodies fused with a toxin or radioactive material, or cells; cancer vaccines developed from cells, parts of cells, or antigens

Delivery routes: Agents may be administered by mouth (orally), injection (subcutaneously or intramuscularly), or injection into a vein (intravenously). Some vaccines are given into the skin (intradermal) or may be placed into the bladder in a liquid form (instillation). Agents may be taken at home or may require a visit to the physician’s office or hospital. The schedule of administration varies with the agent.

How these drugs work: Cancer develops when normal cells change their genetic makeup over some period of time. As these changes occur, protein substances are created on the cell surface that the body does not recognize. An antigen is any substance that causes the immune system of the body to produce antibodies. The body’s activation of the immune system against these unrecognized substances is called an immune response and is the principle of immunotherapy. Antibodies developed outside the body or substances given to encourage the body to develop antibodies against antigens are the foundation for immunotherapy. The immune system includes lymph nodes, the spleen, the tonsils, bone marrow, and white blood cells. Actions of immunotherapy may include increasing a cancer cell’s sensitivity so that the immune system can better attack and kill the cell, preventing the normal cell from becoming malignant, preventing the spread of cancer cells, encouraging the body to repair damaged cells, and changing the activity of normal cells around tumors.

Cytokines are used more frequently than any other type of immunotherapy, as they are employed at some point in most cancers. Because cancer treatments can cause serious side effects and complications, an important part of therapy is side-effect control. White blood cells fight infection in the body and are decreased by chemotherapy drugs, leading to neutropenia. Anemia, which is a decrease in red blood cells responsible for carrying oxygen to cells, can be life-threatening in cancer patients. Erythropoietin stimulates the release of mature red blood cells and may be used as an important part of cancer therapy. Colony-stimulating factors encourage the bone marrow to convert immune cells into neutrophils, critical to fighting infection. Cytokines are naturally produced in the body but can be developed in the laboratory using a system called recombinant deoxyribonucleic acid (DNA) technology. Cytokines can be developed to interact with receptors on immune cells to stimulate the production of red blood cells, for example, or to inhibit or slow cancer-cell growth. While some cytokines are not therapeutic for cancer, they are needed to allow patients to receive their full doses of both immunotherapy and chemotherapy.

A group of cytokines called interleukins are therapeutic for cancer. In 1992, interleukin 2 (IL-2) was the first immunotherapy approved for use alone in treating cancer. IL-2 is used for advanced kidney cancer and melanoma, either alone or in combination with other chemotherapies or immunotherapies. Interleukin stimulates T cells and natural killer cells in the immune system. Interferons, also cytokines, are thought to work by slowing the growth of cancer cells and the blood vessels that supply the tumor. It is also thought that interferons may increase the production of antigens in the cancer cell, making it more visible to antibodies. Natural killer cells may also be boosted by the administration of interferon.

Monoclonal antibodies generally interrupt signals in the cell that cause it to become cancerous. They can be developed to be attracted to the antigen secreted by the cell in order to block its function. Each monoclonal antibody is designed to bind to a specific antigen on the cell. Some monoclonal antibodies attracting significant interest are those that cause the immune system to attack the blood supply of the tumor, a process called antiangiogenesis. Monoclonal antibodies are known as passive immunotherapy because they use antibodies made outside the body in large numbers. Active immunotherapy is when the patient’s own body makes antibodies against antigens, as in the case of vaccine therapy. Monoclonal antibodies are classified as either naked, meaning they work without the addition of another drug or radioactive material, or conjugated, meaning they are joined with another drug, a toxin, or a radioactive particle.

Vaccines are able to trigger the immune system to attack cancer cells with a specific antigen developed in the patient’s body. Clinical trials of these vaccines are ongoing; as of 2014, the US Food and Drug Administration (FDA) has only approved one vaccine to treat cancer directly: sipuleucel-T, which is used to treat asymptomatic metastatic prostate cancer that no longer responds to hormone therapy. Other vaccines, such as the human papillomavirus (HPV) vaccine and the hepatitis B (HBV) vaccine, are more traditional vaccines, delivered to a healthy person in order to prevent future infection by viruses that are known to be linked to some types of cancer.

Some forms of active immunotherapy are not vaccines but may target specific locations within the immune system. Most of these therapies are not approved by the FDA and are available only in clinical research studies. Chimeric antigen receptor (CAR) T-cell therapy involves removing T cells from the patient's blood and genetically modifying them to add antigen receptors, known as chimeric antigen receptors (CARs), to the cell surface. When the modified T cells are reintroduced to the patient's system, the CARs precisely target the cancer cells they were designed to seek out. In another potential form of immunotherapy, immune-system cells known as tumor-infiltrating lymphocytes (TILs), which are found inside some tumors, are extracted and treated with IL-2 in the laboratory, then injected back into the patient. CAR T-cell therapy has shown promising results in some forms of leukemia and lymphoma, while TIL therapy is being tested against a variety of cancers, including melanomas, kidney cancer, and ovarian cancer.

Side effects: Immunotherapy may cause flulike symptoms, including fever, chills, nausea, vomiting, fatigue, headache, low blood count (anemia), inability to fight infection, bone pain, and muscle aches. If the agent is injected, then a rash or swelling may be noted at the site. Blood pressure can drop during administration. More serious but less common side effects include bleeding, difficulty breathing, edema leading to congestive heart failure, heart damage, and severe and potentially life-threatening reactions, such as anaphylaxis.

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