Cancer Biological Therapies

by National Cancer Institute

Key Points

Biological therapies use the body's immune system to fight cancer or to lessen the side effects that may be caused by some cancer treatments.

Biological response modifiers (BRMs) occur naturally in the body and can be produced in the laboratory. BRMs 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.

Biological therapies include interferons, interleukins, colony-stimulating factors, monoclonal antibodies, vaccines, gene therapy, and nonspecific immunomodulating agents.

Biological therapies can cause a number of side effects, which can vary widely from agent to agent and patient to patient.

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 is the immune system and what are its components?

The immune system is a complex network of cells and organs that work together to defend the body against attacks by "foreign" or "non-self" invaders. This network is one of the body's main defenses against infection and disease. The immune system works against diseases, including cancer, in a variety of ways. For example, the immune system may recognize the difference between healthy cells and cancer cells in the body and works to eliminate cancerous cells. However, the immune system does not always recognize cancer cells as "foreign." Also, cancer may develop when the immune system breaks down or does not function adequately. Biological therapies are designed to repair, stimulate, or enhance the immune system's responses.

Immune system cells include the following:

Lymphocytes are a type of white blood cell found in the blood and many other parts of the body. Types of lymphocytes include B cells, T cells, and Natural Killer cells.

• B cells (B lymphocytes) mature into plasma cells that secrete proteins called antibodies (immunoglobulins). Antibodies recognize and attach to foreign substances known as antigens, fitting together much the way a key fits a lock. Each type of B cell makes one specific antibody, which recognizes one specific antigen.

• T cells (T lymphocytes) work primarily by producing proteins called cytokines. Cytokines allow immune system cells to communicate with each other and include lymphokines, interferons, interleukins, and colony-stimulating factors. Some T cells, called cytotoxic T cells, release pore-forming proteins that directly attack infected, foreign, or cancerous cells. Other T cells, called helper T cells, regulate the immune response by releasing cytokines to signal other immune system defenders.

• Natural Killer cells (NK cells) produce powerful cytokines and pore-forming proteins that bind to and kill many foreign invaders, infected cells, and tumor cells. Unlike cytotoxic T cells, they are poised to attack quickly, upon their first encounter with their targets.

Phagocytes are white blood cells that can swallow and digest microscopic organisms and particles in a process known as phagocytosis. There are several types of phagocytes, including monocytes, which circulate in the blood, and macrophages, which are located in tissues throughout the body.

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 alpha, 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's 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 colony-stimulating factors?

Colony-stimulating factors (CSFs) (sometimes called hematopoietic growth factors) usually do not directly affect tumor cells; rather, they encourage bone marrow stem cells to divide and develop into white blood cells, platelets, and red blood cells. Bone marrow is critical to the body's immune system because it is the source of all blood cells.

Stimulation of the immune system by CSFs may benefit patients undergoing cancer treatment. Because anticancer drugs can damage the body's ability to make white blood cells, red blood cells, and platelets, patients receiving anticancer drugs have an increased risk of developing infections, becoming anemic, and bleeding more easily. By using CSFs to stimulate blood cell production, doctors can increase the doses of anticancer drugs without increasing the risk of infection or the need for transfusion with blood products. As a result, researchers have found CSFs particularly useful when combined with high-dose chemotherapy.

About the Author

www.nci.nih.gov
The National Cancer Institute's research programs are extensive and contain many innovative initiatives. I invite you to explore our Web site to find out more about the exciting work being conducted here at NCI and by NCI-supported scientists throughout the country.