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
- 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.
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;
- 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; and
- 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 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 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.
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 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.
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 ?
For most types of cancer, radiation therapy usually is given 5 days a week for 6 or 7 weeks. (When radiation is used for palliative care, the course of treatment is shorter, usually 2 to 3 weeks.) The total dose of radiation and the number of treatments you need will depend on the size, location, and kind of cancer you have, your general health, and other medical treatments you may be receiving.Using many small doses of daily radiation rather than a few large doses helps protect normal body tissues in the treatment area. Weekend rest breaks allow normal cells to recover.
It’s very important that you have all of your scheduled treatments to get the most benefit from your therapy. Missing or delaying treatments can lessen the effectiveness of your radiation treatment.
What Happens During the Treatment Visits ?
Before each treatment, you may need to change into a hospital gown or robe. It’s best to wear clothing that is easy to take off and put on again. In the treatment room, the radiation therapist will use the marks on your skin to locate the treatment area and to position you correctly. You may sit in a special chair or lie down on a treatment table. For each external radiation therapy session, you will be in the treatment room about 15 to 30 minutes, but you will be getting radiation for only about 1 to 5 minutes of that time. Receiving external radiation treatments is painless, just like having an x-ray taken. You will not hear, see, or smell the radiation. The radiation therapist may put special shields (or blocks) between the machine and certain parts of your body to help protect normal tissues and organs. There might also be plastic or plaster forms that help you stay in exactly the right place. You need to remain very still during the treatment so that the radiation reaches only the area where it’s needed and the same area is treated each time. You don’t have to hold your breath — just breathe normally. The radiation therapist will leave the treatment room before your treatment begins. The radiation machine is controlled from a nearby area. You will be watched on a television screen or through a window in the control room. Although you may feel alone, keep in mind that the therapist can see and hear you and even talk with you using an intercom in the treatment room. If you should feel ill or very uncomfortable during the treatment, tell your therapist at once. The machine can be stopped at any time.The machines used for radiation treatments are very large, and they make noises as they move around your body to aim at the treatment area from different angles. Their size and motion may be frightening at first. Remember that the machines are being moved and controlled by your radiation therapist. They are checked constantly to be sure they’re working right. If you have concerns about anything that happens in the treatment room, discuss these concerns with the radiation therapist.
What Can I Do To Take Care of Myself During Therapy ?
Each patient’s body responds to radiation therapy in its own way. That’s why your doctor must plan, and sometimes adjust, your treatment. In addition, your doctor or nurse will give you suggestions for caring for yourself at home that are specific for your treatment and the possible side effects. Nearly all cancer patients receiving radiation therapy need to take special care of themselves to protect their health and to help the treatment succeed. Some guidelines to remember are given on the following pages: Before starting treatment, be sure your doctor knows about any medicines you are taking and if you have any allergies. Do not start taking any medicine (whether prescription or over-the-counter) during your radiation therapy without first telling your doctor or nurse.
- Fatigue is common during radiation therapy. Your body will use a lot of extra energy over the course of your treatment, and you may feel very tired. Be sure to get plenty of rest and sleep as often as you feel the need. It’s common for fatigue to last for 4 to 6 weeks after your treatment has been completed.
- Good nutrition is very important. Try to eat a balanced diet that will prevent weight loss. For patients who have problems with eating or diet planning, the section, “Managing Side Effects,” offers practical tips.
- Check with your doctor before taking vitamin supplements or herbal preparations during treatment.
- Avoid wearing tight clothes such as girdles or close-fitting collars over the treatment area.
- Be extra kind to your skin in the treatment area :
- Ask your doctor or nurse if you may use soaps, lotions, deodorants, sun blocks, medicines, perfumes, cosmetics, talcum powder, or other substances in the treated 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.
- Do not use adhesive tape on treated skin. If bandaging is necessary, use paper tape and apply it outside of the treatment area. Your nurse can help you place dressings so that you can avoid irritating the treated area.
- Do not apply heat or cold (heating pad, ice pack, etc.) to the treated area. Use only lukewarm water for bathing the area.
- 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.
- Protect the treatment area from the sun. Do not apply sunscreens just before a radiation treatment. If possible, cover treated skin (with light clothing) before going outside. Ask your doctor if you should use a sunscreen or a sunblocking product. If so, select one with a protection factor of at least 15 and reapply it often. Ask your doctor or nurse how long after your treatments are completed you should continue to protect the treated skin from sunlight.
- If you have questions, ask your doctor or nurse. They are the only ones who can properly advise you about your treatment, its side effects, home care, and any other medical concerns you may have.
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.
How Are Other People Protected From Radiation While the Implant is in Place ?
Sometimes the radiation source in your implant sends its high energy rays outside your body. To protect others while you are having implant therapy, the hospital will have you stay in a private room. Although the nurses and other people caring for you will not be able to spend a long time in your room, they will give you all of the care you need. You should call for a nurse when you need one, but keep in mind that the nurse will work quickly and speak to you from the doorway more often than from your bedside. In most cases, your urine and stool will contain no radioactivity unless you are having unsealed internal radiation therapy. There also will be limits on visitors while your implant is in place. Children younger than 18 or pregnant women should not visit patients who are having internal radiation therapy. Be sure to tell your visitors to ask the hospital staff for any special instructions before they come into your room. Visitors should sit at least 6 feet from your bed and the radiation oncology staff will determine how long your visitors may stay. The time can vary from 30 minutes to several hours per day. In some hospitals a rolling lead shield is placed beside the bed and kept between the patient and visitors or staff members.
What Are the Side Effects of Internal Radiation Therapy?
The side effects of implant therapy depend on the area being treated. You are not likely to have severe pain or feel ill during implant therapy. However, if an applicator is holding your implant in place, it may be somewhat uncomfortable. If you need it, the doctor will order medicine to help you relax or to relieve pain. If general anesthesia was used while your implant was put in place, you may feel drowsy, weak, or nauseated but these effects do not last long. If necessary, medications can be ordered to relieve nausea. Be sure to tell the nurse about any symptoms that concern you. In Section 4, “Managing Side Effects,” you will find tips on how to deal with problems that might occur after implant therapy.
How Long Does the Implant Stay in Place ?
Your doctor will decide the amount of time that an implant is to be left in place. It depends on the dose (amount) of radioactivity needed for effective treatment. Your treatment schedule will depend on the type of cancer, where it is located, your general health, and other cancer treatments you have had. Depending on where the implant is placed, you may have to keep it from shifting by staying in bed and lying fairly still.Temporary implants may be either low dose-rate (LDR) or high dose-rate (HDR). Low dose-rate implants are left in place for several days; high dose-rate implants are removed after a few minutes.For some cancer sites, the implant is left in place permanently. If your implant is permanent, you may need to stay in your hospital room away from other people for a few days while the radiation is most active. The implant becomes less radioactive each day; by the time you are ready to go home, the radiation in your body will be much weaker. Your doctor will advise you if there are any special precautions you need to use at home.
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.
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 ?
Most patients return to the radiation oncologist for regular follow-up visits. Others are referred to their original doctor, to a surgeon, or to a medical oncologist. Your followup care will depend on the kind of cancer that was treated and on other treatments that you had or may need.
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
Following are some questions that you may want to ask your doctor after you have finished your radiation therapy
- How often do I need to return for checkups?
- Why do I need more x-rays, CT-scans, blood tests, and so on? What will these tests tell us?
- Will I need chemotherapy, surgery, or other treatments?
- How and when will you know if I’m cured of cancer?
- What are the chances that it will come back?
- How soon can I go back to my regular activities? Work? Sexual activity? Sports?
- Do I need to take any special precautions like staying out of the sun or avoiding people with infectious diseases?
- Do I need a special diet?
- Should I exercise?
- Can I wear a prosthesis?
- Can I have reconstructive surgery ? How soon can I schedule it?
It’s a good idea to write down the questions you want to ask your doctor. Use the “Notes” page at the back of this booklet for your questions and take it with you when you have your appointment with the doctor. Some patients find that it’s helpful to take a family member with them to help remember what the doctor says.
How Can I Help Myself After Radiation Therapy
Patients who have had radiation therapy need to continue some of the special care they used during treatment, at least for a short while. For instance, you may have skin problems for several weeks after your treatments end. Continue to be gentle with skin in the treatment area until all signs of irritation are gone. Don’t try to scrub off the marks in your treatment area. If tattoos were used to mark the treatment area, they are permanent and will not wash off. Your nurse can answer questions about skin care and help you with other concerns you may have after your treatment has been completed. You may find that you still need extra rest after your therapy is over while your healthy tissues are recovering and rebuilding. Keep taking naps as needed and try to get more sleep at night. It may take some time to get your strength back, so resume your normal schedule of activities gradually. If you feel that you need emotional or social support, ask your doctor, nurse, or a social worker for information about support groups or other ways to express your feelings and concerns.
When Should I Call the Doctor
After treatment for cancer, you’re likely to be more aware of your body and to notice even slight changes in how you feel from day to day. The doctor will want to know if you are having any unusual symptoms. Promptly tell your doctor about:
- A pain that doesn’t go away, especially if it’s always in the same place.
- 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.
We hope that the information in this booklet will help you understand how radiation therapy is used to treat cancer. If you know what to expect when you go for your treatments, you may not feel as anxious. Remember to talk with your nurse, doctor, or other members of your health care team whenever you have questions or feel that you need more information.