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Biological Therapies: Using the Immune System To Treat Cancer

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.

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 disease. It works against disease, 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 work to eliminate those that become cancerous. Cancer may develop when the immune system breaks down or is not functioning 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 antibodies (immunoglobulins), the proteins that recognize and attach to foreign substances known as antigens. Each type of B cell makes one specific antibody, which recognizes one specific antigen.
  • T cells (T lymphocytes) directly attack infected, foreign, or cancerous cells. T cells also regulate the immune response by signaling other immune system defenders. T cells work primarily by producing proteins called lymphokines.
  • Natural Killer cells (NK cells) produce powerful chemical substances that bind to and kill any foreign invader. They attack without first having to recognize a specific antigen.


Monocytes are white blood cells that can swallow and digest microscopic organisms and particles in a process known as phagocytosis. Monocytes can also travel into tissue and become macrophages, or “big eaters.”

Cells in the immune system secrete two types of proteins: antibodies and cytokines. Antibodies respond to antigens by latching on to, or binding with, the antigens. Specific antibodies match specific antigens, fitting together much the way a key fits a lock. Cytokines are substances produced by some immune system cells to communicate with other cells. Types of cytokines include lymphokines, interferons, interleukins, and colony-stimulating factors. Cytotoxic cytokines are released by a type of T cell called a cytotoxic T cell. These cytokines attack cancer cells directly.


Nonspecific Immunomodulating Agents



Biological Response Modifier

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, and vaccines. Researchers continue to discover new BRMs, learn more about how they function, and 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 cancer cells’ growth patterns to promote behavior like that of healthy cells;
  • 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; and

Some BRMs are a standard part of treatment for certain types of cancer, while others are being studied in clinical trials (research studies with people). 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.


Interferons (IFN)

Interferons 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 metastatic 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.


Interleukins (IL)

Like interferons, interleukins 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 colorectal, ovarian, lung, brain, breast, prostate, some leukemias, and some lymphomas.


Colony-Stimulating Factors (CSFs)

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. The CSFs’ stimulation of the immune system 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.

Some examples of CSFs and their use in cancer therapy are as follows:

  • G-CSF (filgrastim) and GM-CSF (sargramostim) can increase the number of white blood cells, thereby reducing the risk of infection in patients receiving chemotherapy. G-CSF and GM-CSF can also stimulate the production of stem cells in preparation for stem cell or bone marrow transplants;
  • Erythropoietin can increase the number of red blood cells and reduce the need for red blood cell transfusions in patients receiving chemotherapy; and
  • Oprelvekin can reduce the need for platelet transfusions in patients receiving chemotherapy.

Researchers are studying CSFs in clinical trials to treat some types of leukemia, metastatic colorectal cancer, melanoma, lung cancer, and other types of cancer.


Monoclonal Antibodies (MOABs)

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 the cancer cell being treated. MOABs are made by injecting human cancer cells into mice so that their immune systems will make antibodies against these cancer cells. The mouse cells producing the antibodies are then removed and fused 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 may help destroy cancer cells in bone marrow that has been removed from a patient in preparation for a bone marrow transplant.

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 monoclonal antibodies that have been approved by the FDA. Rituxan is used for the treatment of B-cell non-Hodgkin’s lymphoma that has returned after a period of improvement or has not responded to chemotherapy. Herceptin is used to treat metastatic breast cancer in patients with tumors that produce excess amounts of a protein called HER–2. (Approximately 25 percent of breast cancer tumors produce excess amounts of HER–2.) Researchers are testing MOABs in clinical trials to treat lymphomas, leukemias, colorectal cancer, lung cancer, brain tumors, prostate cancer, and other types of cancer.


Cancer Vaccines

Cancer vaccines are another form of biological therapy currently under study. Vaccines for infectious diseases, such as measles, mumps, and tetanus, 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 cells to produce more plasma cells, which make antibodies. T cells that recognize the infectious agent also multiply. These activated T cells later remember the exposure. The next time the agent enters the body, cells in the immune system are already prepared to respond and stop the infection.For cancer treatment, researchers are developing vaccines that may encourage the patient’s immune system to recognize cancer cells. These vaccines may help the body reject tumors and prevent cancer from recurring. In contrast to vaccines against infectious diseases, cancer vaccines are designed to be injected after the disease is diagnosed, rather than before it develops. Cancer vaccines given when the tumor is small may be able to eradicate the cancer. Early cancer vaccine clinical trials (research studies with people) involved mainly patients with melanoma. Currently, cancer vaccines are also being studied in the treatment of many other types of cancer, including lymphomas and cancers of the kidney, breast, ovary, prostate, colon, and rectum. Researchers are also investigating ways that cancer vaccines can be used in combination with other BRMs.


Side Effects

Like other forms of cancer treatment, biological therapies can cause a number of side effects, which can vary widely from patient to patient. Rashes or swelling may develop at the site where the BRMs are injected. Several BRMs, including interferons and interleukins, may cause flu-like symptoms including fever, chills, nausea, vomiting, and appetite loss. Fatigue is another common side effect of BRMs. Blood pressure may also be affected. The side effects of IL–2 can often be severe, depending on the dosage given. Patients need to be closely monitored during treatment. Side effects of CSFs may include bone pain, fatigue, fever, and appetite loss. The side effects of MOABs vary, and serious allergic reactions may occur. Cancer vaccines can cause muscle aches and fever.


How Long Does the Treatment Take ?




What Happens During the Treatment Visits ?



What Can I Do To Take Care of Myself During Therapy ?


  • Be extra kind to your skin in the treatment area :
  • Wear loose, soft cotton clothing over the treated area.
  • Do not wear starched or stiff clothing over the treated area.
  • Do not scratch, rub, or scrub treated skin.
  • Use an electric shaver if you must shave the treated area but only after checking with your doctor or nurse. Do not use a preshave lotion or hair removal products on the treated area.


Internal Radiation Therapy: What to Expect When Is Internal Radiation Therapy Used ?

Your doctor may decide that a high dose of radiation given to a small area of your body is the best way to treat your cancer. Internal radiation therapy allows the doctor to give a higher total dose of radiation in a shorter time than is possible with external treatment. Internal radiation therapy places the radiation source as close as possible to the cancer cells. Instead of using a large radiation machine, the radioactive material, sealed in a thin wire, catheter, or tube (implant), is placed directly into the affected tissue. This method of treatment concentrates the radiation on the cancer cells and lessens radiation damage to some of the normal tissue near the cancer. Some of the radioactive substances used for internal radiation treatment include cesium, iridium, iodine, phosphorus, and palladium.Internal radiation therapy may be used for cancers of the head and neck, breast, uterus, thyroid, cervix, and prostate. Your doctor may suggest using both internal and external radiation therapy.In this booklet, ‘internal radiation treatment’ refers to implant radiation. Health professionals prefer to use the term “brachytherapy” for implant radiation therapy. You may hear your doctor or nurse use the terms, interstitial radiation or intracavitary radiation; each is a form of internal radiation therapy. Sometimes radioactive implants are called “capsules” or “seeds.”


How Is the Implant Placed in the Body ?

The type of implant and the method of placing it depend on the size and location of the cancer. Implants may be put right into the tumor (interstitial radiation), in special applicators inside a body cavity (intracavitary radiation) or passage (intraluminal radiation), on the surface of a tumor, or in the area from which the tumor has been removed. Implants may be removed after a short time or left in place permanently. If they are to be left in place, the radioactive substance used will lose radiation quickly and become non-radioactive in a short time. When interstitial radiation is given, the radiation source is placed in the tumor in catheters, seeds, or capsules. When intracavitary radiation is used, a container or applicator of radioactive material is placed in a body cavity such as the uterus. In surface brachytherapy the radioactive source is sealed in a small holder and placed in or against the tumor. In intraluminal brachytherapy the radioactive source is placed in a body lumen or tube, such as the bronchus or esophagus. Internal radiation also may be given by injecting a solution of radioactive substance into the bloodstream or a body cavity. This form of radiation therapy may be called unsealed internal radiation therapy. For most types of implants, you will need to be in the hospital. You will be given general or local anesthesia so that you will not feel any pain when the doctor places the holder for the radioactive material in your body. In many hospitals, the radioactive material is placed in its holder or applicator after you return to your room so that other patients, staff, and visitors are not exposed to radiation.





What Are the Side Effects of Internal Radiation Therapy?



How Long Does the Implant Stay in Place ?



What Happens After the Implant Is Removed ?

Usually, an anesthetic is not needed when the doctor removes a temporary implant. Most can be taken out right in the patient’s hospital room. Once the implant is removed, there is no radioactivity in your body. The hospital staff and your visitors will no longer have to limit the time they stay with you.Your doctor will tell you if you need to limit your activities after you leave the hospital. Most patients are allowed to do as much as they feel like doing. You may need some extra sleep or rest breaks during your days at home, but you should feel stronger quickly.The area that has been treated with an implant may be sore or sensitive for some time. If any particular activity such as sports or sexual intercourse cause irritation in the treatment area, your doctor may suggest that you limit these activities for a while.


Followup Care

What Does “Followup” Mean ?

Once you have completed your radiation treatments, it is important for your doctor to monitor the results of your therapy at regularly scheduled visits. These checkups are necessary to deal with radiation side effects and to detect any signs of recurrent disease. During these checkups your doctor will examine you and may order some lab tests and x-rays. The radiation oncologist also will want to see you for followup after your treatment ends and will coordinate followup care with your doctor. Followup care might include more cancer treatment, rehabilitation, and counseling. Taking good care of yourself is also an important part of following through after radiation treatments.


Who Provides Care After Therapy ?



What Other Care Might Be Needed ?

Just as every patient is different, followup care varies. Your doctor will prescribe and schedule the followup care that you need. Don’t hesitate to ask about the tests or treatments that your doctor orders. Try to learn all the things you need to do to take good care of yourself.


Questions to ask


  • How often do I need to return for checkups?
  • Will I need chemotherapy, surgery, or other treatments?
  • What are the chances that it will come back?
  • Do I need a special diet?
  • Should I exercise?
  • Can I wear a prosthesis?



How Can I Help Myself After Radiation Therapy



When Should I Call the Doctor


  • New or unusual lumps, bumps, or swelling.
  • Nausea, vomiting, diarrhea, or loss of appetite.
  • Unexplained weight loss.
  • A fever or cough that doesn’t go away.
  • Unusual rashes, bruises, or bleeding.
  • Any symptoms that you are concerned about.
  • Any other warning signs mentioned by your doctor or nurse.


