More information about cancer can be found at the National Cancer Institute website http://www.cancer.gov

Immunotherapy

Biological Therapies for Cancer: Questions and Answers

A fact sheet that provides an overview of how the immune system functions and describes the actions of biological therapies.

Biological Therapy

An introduction to biological therapy to help patients prepare to receive it for cancer treatment or managing side effects.

What is biological therapy? Biological therapy (sometimes called immunotherapy, biotherapy or biological response modifier therapy is a relatively new addition to the family of cancer treatments that also includes surgery, chemotherapy, and radiation therapy. Biological therapies use the body's immune system, either directly or indirectly, to fight cancer or to lessen the side effects that may be caused by some cancer treatments.

What are biological response modifiers, and how can they be used to treat cancer? Some antibodies, cytokines, and other immune system substances can be produced in the laboratory for use in cancer treatment. These substances are often called biological response modifiers (BRMs). They alter the interaction between the body's immune defenses and cancer cells to boost, direct, or restore the body's ability to fight the disease. BRMs include interferons, interleukins, colony-stimulating factors, monoclonal antibodies, vaccines, gene therapy, and nonspecific immunomodulating agents.

Researchers continue to discover new BRMs, to learn more about how they function, and to develop ways to use them in cancer therapy. Biological therapies may be used to:

  • Stop, control, or suppress processes that permit cancer growth.
  • Make cancer cells more recognizable and, therefore, more susceptible to destruction by the immune system.
  • Boost the killing power of immune system cells, such as T cells, NK cells, and macrophages.
  • Alter the growth patterns of cancer cells to promote behavior like that of healthy cells.
  • Block or reverse the process that changes a normal cell or a precancerous cell into a cancerous cell.
  • Enhance the body's ability to repair or replace normal cells damaged or destroyed by other forms of cancer treatment, such as chemotherapy or radiation.
  • Prevent cancer cells from spreading to other parts of the body.

Some BRMs are a standard part of treatment for certain types of cancer, while others are being studied in clinical trials (research studies). BRMs are being used alone or in combination with each other. They are also being used with other treatments, such as radiation therapy and chemotherapy.

What are interferons? Interferons (IFNs) are types of cytokines that occur naturally in the body. They were the first cytokines produced in the laboratory for use as BRMs. There are three major types of interferons — interferon beta and interferon gamma; interferon alpha is the type most widely used in cancer treatment.

Researchers have found that interferons can improve the way a cancer patient's immune system acts against cancer cells. In addition, interferons may act directly on cancer cells by slowing their growth or promoting their development into cells with more normal behavior. Researchers believe that some interferons may also stimulate NK cells, T cells, and macrophages, boosting the immune system's anticancer function.

The U.S. Food and Drug Administration (FDA) has approved the use of interferon alpha for the treatment of certain types of cancer, including hairy cell leukemia, melanoma, chronic myeloid leukemia, and AIDS-related Kaposi's sarcoma. Studies have shown that interferon alpha may also be effective in treating other cancers such as kidney cancer and non-Hodgkin lymphoma. Researchers are exploring combinations of interferon alpha and other BRMs or chemotherapy in clinical trials to treat a number of cancers.

What are interleukins? Like interferons, interleukins (ILs) are cytokines that occur naturally in the body and can be made in the laboratory. Many interleukins have been identified; interleukin-2 (IL–2 or aldesleukin) has been the most widely studied in cancer treatment. IL–2 stimulates the growth and activity of many immune cells, such as lymphocytes, that can destroy cancer cells. The FDA has approved IL–2 for the treatment of metastatic kidney cancer and metastatic melanoma.

Researchers continue to study the benefits of interleukins to treat a number of other cancers, including leukemia, lymphoma, and brain, colorectal, ovarian, breast, and prostate cancers.

What are cancer vaccines? Cancer vaccines are another form of biological therapy currently under study. Vaccines for infectious diseases, such as measles, mumps, and tetanus, are injected into a person before the disease develops. These vaccines are effective because they expose the body's immune cells to weakened forms of antigens that are present on the surface of the infectious agent. This exposure causes the immune system to increase production of plasma cells that make antibodies specific to the infectious agent. The immune system also increases production of T cells that recognize the infectious agent. These activated immune cells remember the exposure, so that the next time the agent enters the body, the immune system is already prepared to respond and stop the infection.

Researchers are developing vaccines that may encourage the patient's immune system to recognize cancer cells. Cancer vaccines are designed to treat existing cancers (therapeutic vaccines) or to prevent the development of cancer (prophylactic vaccines). Therapeutic vaccines are injected in a person after cancer is diagnosed. These vaccines may stop the growth of existing tumors, prevent cancer from recurring, or eliminate cancer cells not killed by prior treatments. Cancer vaccines given when the tumor is small may be able to eradicate the cancer. On the other hand, prophylactic vaccines are given to healthy individuals before cancer develops. These vaccines are designed to stimulate the immune system to attack viruses that can cause cancer. By targeting these cancer-causing viruses, doctors hope to prevent the development of certain cancers.

Early cancer vaccine clinical trials involved mainly patients with melanoma. Therapeutic vaccines are also being studied in the treatment of many other types of cancer, including lymphoma, leukemia, and cancers of the brain, breast, lung, kidney, ovary, prostate, pancreas, colon, and rectum. Researchers are also studying prophylactic vaccines to prevent cancers of the cervix and liver. Moreover, scientists are investigating ways that cancer vaccines can be used in combination with other BRMs.

What are monoclonal antibodies? Researchers are evaluating the effectiveness of certain antibodies made in the laboratory called monoclonal antibodies (MOABs or MoABs). These antibodies are produced by a single type of cell and are specific for a particular antigen. Researchers are examining ways to create MOABs specific to the antigens found on the surface of various cancer cells.

To create MOABs, scientists first inject human cancer cells into mice. In response, the mouse immune system makes antibodies against these cancer cells. The scientists then remove the mouse plasma cells that produce antibodies, and fuse them with laboratory-grown cells to create “hybrid” cells called hybridomas. Hybridomas can indefinitely produce large quantities of these pure antibodies, or MOABs.

MOABs may be used in cancer treatment in a number of ways:

  • MOABs that react with specific types of cancer may enhance a patient's immune response to the cancer.
  • MOABs can be programmed to act against cell growth factors, thus interfering with the growth of cancer cells.
  • MOABs may be linked to anticancer drugs, radioisotopes (radioactive substances), other BRMs, or other toxins. When the antibodies latch onto cancer cells, they deliver these poisons directly to the tumor, helping to destroy it.

MOABs carrying radioisotopes may also prove useful in diagnosing certain cancers, such as colorectal, ovarian, and prostate.

Rituxan® (rituximab) and Herceptin® (trastuzumab) are examples of MOABs that have been approved by the FDA. Rituxan is used for the treatment of non-Hodgkin lymphoma. Herceptin is used to treat metastatic breast cancer in patients with tumors that produce excess amounts of a protein called HER–2. (More information about Herceptin is available in the National Cancer Institute (NCI) fact sheet Herceptin® (Trastuzumab): Questions and Answers, which can be found at http://www.cancer.gov/cancertopics/factsheet/Therapy/herceptin on the Internet.) In clinical trials, researchers are testing MOABs to treat lymphoma, leukemia, melanoma, and cancers of the brain, breast, lung, kidney, colon, rectum, ovary, prostate, and other areas.

What are nonspecific immunomodulating agents? Nonspecific immunomodulating agents are substances that stimulate or indirectly augment the immune system. Often, these agents target key immune system cells and cause secondary responses such as increased production of cytokines and immunoglobulins. Two nonspecific immunomodulating agents used in cancer treatment are bacillus Calmette-Guerin (BCG) and levamisole.

BCG, which has been widely used as a tuberculosis vaccine, is used in the treatment of superficial bladder cancer following surgery. BCG may work by stimulating an inflammatory, and possibly an immune, response. A solution of BCG is instilled in the bladder and stays there for about 2 hours before the patient is allowed to empty the bladder by urinating. This treatment is usually performed once a week for 6 weeks. Levamisole is sometimes used along with fluorouracil (5–FU) chemotherapy in the treatment of stage III (Dukes–C) colon cancer following surgery. Levamisole may act to restore depressed immune function.

Docetaxel US brand name: Taxotere

Taxotere is a semi-synthetic, second-generation taxane derived from a compound found in the European yew tree Taxus baccata. Docetaxel displays potent and broad antineoplastic properties; it binds to and stabilizes tubulin, thereby inhibiting microtubule disassembly which results in cell- cycle arrest at the G2/M phase and cell death. This agent also inhibits pro-angiogenic factors such as vascular endothelial growth factor (VEGF) and displays immunomodulatory and pro-inflammatory properties by inducing various mediators of the inflammatory response. Docetaxel has been studied for use as a radiation-sensitizing agent. Check for active clinical trials or closed clinical trials using this agent. (NCI Thesaurus)

Carboplatin

A second-generation platinum compound with a broad spectrum of antineoplastic properties. Carboplatin contains a platinum atom complexed with two ammonia groups and a cyclobutane-dicarboxyl residue. This agent is activated intracellularly to form reactive platinum complexes that bind to nucleophilic groups such as GC-rich sites in DNA, thereby inducing intrastrand and interstrand DNA cross-links, as well as DNA-protein cross-links. These carboplatin-induced DNA and protein effects result in apoptosis and cell growth inhibition. This agent possesses tumoricidal activity similar to that of its parent compound, cisplatin, but is more stable and less toxic. Check for active clinical trials or closed clinical trials using this agent. (NCI Thesaurus)

Imatinib US brand name: Gleevec

The mesylate salt of imatinib, a tyrosine kinase inhibitor with antineoplastic activity. Imatinib binds to an intracellular pocket located within tyrosine kinases (TK), thereby inhibiting ATP binding and preventing phosphorylation and the subsequent activation of growth receptors and their downstream signal transduction pathways. This agent inhibits TK encoded by the bcr-abl oncogene as well as receptor TKs encoded by the c-kit and platelet-derived growth factor receptor (PDGFR) oncogenes. Inhibition of the bcr-abl TK results in decreased proliferation and enhanced apoptosis in malignant cells of Philadelphia-positive (Ph+) hematological malignancies such as CML and ALL; effects on c-kit TK activity inhibit mast-cell and cellular proliferation in those diseases overexpressing c-kit, such as mastocytosis and gastrointestinal stromal tumor (GIST). Check for active clinical trials or closed clinical trials using this agent. (NCI Thesaurus)

Angiogenesis Inhibitors Therapy

A fact sheet that describes the process of eliminating the blood supply to tumors. Lists the cancers in which this approach is being tested.

Targeted Cancer Therapies

This NCI fact sheet describes targeted cancer therapies, which are drugs that block the growth and spread of cancer by interfering with specific molecules involved in carcinogenesis (the process by which normal cells are transformed into cancer cells) and tumor growth.

Chemotherapy

Radiation Therapy for Cancer: Questions and Answers

A fact sheet that defines the different types of radiation therapy and discusses scientific advances that improve the effectiveness of this treatment.

Radiation Therapy and You: Support for People With Cancer

Information about what to expect during radiation therapy, including the general effects of treatment and how to deal with specific side effects.

Radiation Therapy Side Effects Fact Sheets

Radiation therapy fact sheets that help patients understand their treatment and manage side effects. The fact sheets (also available in audio) have patient testimonials, tips from healthcare providers, and questions to ask providers.

Bone Marrow Transplantation and Peripheral Blood Stem Cell Transplantation

A fact sheet that explains the step-by-step procedures of two types of transplantations used with high-dose chemotherapy, including their risks and benefits.

Radiation Therapy

Radiation Therapy for Cancer: Questions and Answers

A fact sheet that defines the different types of radiation therapy and discusses scientific advances that improve the effectiveness of this treatment.

Radiation Therapy and You: Support for People With Cancer

Information about what to expect during radiation therapy, including the general effects of treatment and how to deal with specific side effects.

Radiation Therapy Side Effects Fact Sheets

Radiation therapy fact sheets that help patients understand their treatment and manage side effects. The fact sheets (also available in audio) have patient testimonials, tips from healthcare providers, and questions to ask providers.

Bone Marrow Transplantation and Peripheral Blood Stem Cell Transplantation

A fact sheet that explains the step-by-step procedures of two types of transplantations used with high-dose chemotherapy, including their risks and benefits.