Immunologic Therapies

Immunologic Therapies

 

Definition

Immunologic therapy is the treatment of disease using medicines that boost the body's natural immune response.

Purpose

Immunologic therapy is used to improve the immune system's natural ability to fight diseases such as cancer, hepatitis and AIDS. These drugs may also be used to help the body recover from immunosuppression resulting from treatments such as chemotherapy or radiation therapy.

Description

Most drugs in this category are synthetic versions of substances produced naturally in the body. In their natural forms, these substances help defend the body against disease. For example, aldesleukin (Proleukin) is an artificially made form of interleukin-2, which helps white blood cells work. Aldesleukin is administered to patients with kidney cancers and skin cancers that have spread to other parts of the body. Filgrastim (Neupogen) and sargramostim (Leukine) are versions of natural substances called colony stimulating factors, which drive the bone marrow to make new white blood cells. Another type of drug, epoetin (Epogen, Procrit), is a synthetic version of human erythropoietin that stimulates the bone marrow to make new red blood cells. Thrombopoietin stimulates the production of platelets, disk-shaped bodies in the blood that are important in clotting. Interferons are substances the body produces naturally using immune cells to fight infections and tumors. The synthetic interferons carry brand names such as Alferon, Roferon or Intron A. Some of the interferons that are currently in use as drugs are Recombinant Interferon Alfa-2a, Recombinant Interferon Alfa-2b, interferon alfa-n1 and Interferon Alfa-n3. Alfa interferons are used to treat hairy cell leukemia, malignant melanoma and AIDs-related Kaposi's sarcoma. In addition interferons are also used for other conditions such as laryngeal papillomatosis, genital warts and certain types of hepatitis.

Recommended dosage

The recommended dosage depends on the type of immunologic therapy. For some medicines, the physician will decide the dosage for each patient, taking into account a patient's weight and whether he/she is taking other medicines. Some drugs used in immunologic therapy are given only in a hospital, under a physician's supervision. For those that patients may give themselves, check with the physician who prescribed the medicine or the pharmacist who filled the prescription for the correct dosage.
Most of these drugs come in injectable form. These drugs are generally administered by the cancer care provider.

Precautions

Aldesleukin

This medicine may temporarily increase the chance of getting infections. It may also lower the number of platelets in the blood, and thus possibly interfering with the blood's ability to clot. Taking these precautions may reduce the chance of such problems:
  • Avoid people with infections, if possible.
  • Be alert to signs of infection, such as fever, chills, sore throat, pain in the lower back or side, cough, hoarseness, or painful or difficulty with urination. If any of these symptoms occur, get in touch with a physician immediately.
  • Be alert to signs of bleeding problems, such as black, tarry stools, tiny red spots on the skin, blood in the urine or stools, or any other unusual bleeding or bruising.
  • Take care to avoid cuts or other injuries. Be especially careful when using knives, razors, nail clippers and other sharp objects. Check with a dentist for the best ways to clean the teeth and mouth without injuring the gums. Do not have dental work done without checking with a physician.
  • Wash hands frequently, and avoid touching the eyes or inside of the nose unless the hands have just been washed.
Aldesleukin may make some medical conditions worse, such as chickenpox, shingles (herpes zoster), liver disease, lung disease, heart disease, underactive thyroid, psoriasis, immune system problems and mental problems. The medicine may increase the chance of seizures (convulsions) in people who are prone to having them. Also, the drug's effects may be greater in people with kidney disease, because their kidneys are slow to clear the medicine from their bodies.

Colony stimulating factors

Certain drugs used in treating cancer reduce the body's ability to fight infections. Although colony stimulating factors help restore the body's natural defenses, the process takes time. Getting prompt treatment for infections is important, even while taking this medicine. Call the physician at the first sign of illness or infection, such as a sore throat, fever or chills.
People with certain medical conditions could have problems if they take colony stimulating factors. People who have kidney disease, liver disease or conditions caused by inflammation or immune system problems can worsen these problems with colony stimulating factors. Those who have heart disease may be more likely to experience side effects such as water retention and heart rhythm problems while taking these drugs. Finally, patients who have lung disease might increase their chances of suffering from shortness of breath. Those who have any of these medical conditions should check with their personal physicians before using colony stimulating factors.

Epoetin

Epoetin is a medicine that may cause seizures (convulsions), especially in people who are prone to having them. No one who takes these drugs should drive, use machines or do anything considered dangerous in case of a seizure.
Epoetin helps the body make new red blood cells, but it is not effective unless there is adequate iron in the body. The physician may recommend taking iron supplements or certain vitamins that help supply the body with iron. It is necessary to follow the physician's advice in this instance—recommendations for iron in this case, as with any supplements should only come from a physician.
In studies of laboratory animals, epoetin taken during pregnancy caused birth defects, including damage to the bones and spine. However, the drug has not been reported to cause problems in human babies whose mothers take it. Women who are pregnant or who may become pregnant should check with their physicians for the most up-to-date information on the safety of taking this medicine during pregnancy.
People with certain medical conditions may have problems if they take this medicine. For example, the chance of side effects may be greater in people with high blood pressure, heart or blood vessel disease or a history of blood clots. Epoetin may not work properly in people who have bone problems or sickle cell anemia.

Interferons

Interferons can add to the effects of alcohol and other drugs that slow down the central nervous system, such as antihistamines, cold medicine, allergy medicine, sleep aids, medicine for seizures, tranquilizers, some pain relievers, and muscle relaxants. They may also add to the effects of anesthetics, including those used for dental procedures. Those taking interferons should check with their physicians before taking any of the above.
Some people experience dizziness, unusual fatigue, or become less alert than usual while being treated with these drugs. Because of these possible problems, anyone who takes these drugs should not drive, use machines or do anything else considered dangerous until they have determined how the drugs affect them.
Interferons often cause flu-like symptoms, including fever and chills. The physician who prescribes this medicine may recommend taking acetaminophen (Tylenol) before—and sometimes after—each dose to keep the fever from getting too high. If the physician recommends this, follow instructions carefully.
Like aldesleukin, interferons may temporarily increase the chance of getting infections and lower the number of platelets in the blood, leading to clotting problems. To help prevent these problems, follow the precautions for reducing the risk of infection and bleeding listed for aldesleukin.
People who have certain medical conditions may have problems if they take interferons. For example, the drugs may worsen some medical conditions, including heart disease, kidney disease, liver disease, lung disease, diabetes, bleeding problems and mental problems. In people who have overactive immune systems, these drugs can even increase the activity of the immune system. People who have shingles or chickenpox, or who have recently been exposed to chickenpox may increase their risk of developing severe problems in other parts of the body if they take interferons. People with a history of seizures or mental problems could at risk if taking interferon.
In teenage women, interferons may cause changes in the menstrual cycle. Young women should discuss this possibility with their physicians. Older people may be more sensitive to the effects of interferons. This may increase the chance of side effects.
These drugs are not known to cause fetal death, birth defects or other problems in humans when taken during pregnancy. Women who are pregnant or who may become pregnant should ask their physicians for the latest information on the safety of taking these drugs during pregnancy.
Women who are breastfeeding their babies may need to stop while taking this medicine. Whether interferons pass into breast milk is not known. Because of the chance of serious side effects to the baby, breastfeeding while taking interferon is discouraged. Check with a physician for advice.

General precautions for all types of immunologic therapy

Regular physician visits are necessary during immunologic therapy treatment. This gives the physician a chance to make sure the medicine is working and to check for unwanted side effects.
Anyone who has had unusual reactions to drugs used in immunologic therapy should let the physician know before resuming the drugs. Any allergies to foods, dyes, preservatives, or other substances should also be reported.

Side effects

Aldesleukin

In addition to its helpful effects, this medicine may cause serious side effects. Generally, it is given only in a hospital, where medical professionals can watch for early signs of problems. Medical tests might be performed to check for unwanted effects.
Anyone who has breathing problems, fever or chills while being given aldesleukin should check with a physician immediately.
Other side effects should be brought to a physician's attention as soon as possible:
  • dizziness
  • drowsiness
  • confusion
  • agitation
  • depression
  • nausea and vomiting
  • diarrhea
  • sores in the mouth and on the lips
  • tingling of hands or feet
  • decrease in urination
  • unexplained weight gain of five or more pounds
Some side effects are usually temporary and do not need medical attention unless they are bothersome. These include dry skin; itchy or burning skin rash or redness followed by peeling; loss of appetite; and a general feeling of illness or discomfort.

Colony stimulating factors

As this medicine starts to work, the patient might experience mild pain in the lower back or hips. This is nothing to cause undue concern, and will usually go away within a few days. If the pain is intense or causes discomfort, the physician may prescribe a painkiller.
Other possible side effects include headache, joint or muscle pain and skin rash or itching. These side effects tend to disappear as the body adjusts to the medicine, and do not need medical treatment. If they continue, or they interfere with normal activities, check with a physician.

Epoetin

This medicine may cause flu-like symptoms, such as muscle aches, bone pain, fever, chills, shivering, and sweating, within a few hours after it is taken. These symptoms usually go away within 12 hours. If they do not, or if they are troubling, check with a physician. Other possible side effects that do not need medical attention are diarrhea, nausea or vomiting and fatigue or weakness.
Certain side effects should be brought to a physician's attention as soon as possible. These include headache, vision problems, increased blood pressure, fast heartbeat, weight gain and swelling of the face, fingers, lower legs, ankles or feet.
Anyone who has chest pain or seizures after taking epoetin should seek professional emergency medical attention immediately.

Interferons

This medicine may cause temporary hair loss (alopecia). While upsetting, it is not a sign that something is seriously wrong. The hair should grow back normally after treatment ends.
As the body adjusts to the medicine many other side effects usually go away during treatment. These include flu-like symptoms, taste alteration, loss of appetite (anorexia), nausea and vomiting, skin rash, and unusual fatigue. If these problems persist, or if they interfere with normal life, check with a physician.
A few more serious side effects should be brought to a physician's attention as soon as possible:
  • confusion
  • difficulty thinking or concentrating
  • nervousness
  • depression
  • sleep problems
  • numbness or tingling in the fingers, toes and face

General caution regarding side effects for all types of immunologic therapy

Other side effects are possible with any type of immunologic therapy. Anyone who has unusual symptoms during or after treatment with these drugs should should contact the physician immediately.

Interactions

Anyone who has immunologic therapy should let the physician know all other medicines being taken. Some combinations of drugs may interact, that can increase or decrease the effects of one or both drugs or can increase the likelihood of side effects. Consultation with a physician is highly recommended to get the insight on whether the possible interactions can interfere with drug therapy or cause harmful effects.

Immunoprevention

Considering that most of the biological modifiers such as cytokines elicit immune response that inhibit incipient tumors before they are clinically evident, immunoprevention has been proposed as a recent strategy for combating cancer. Treatment involving immune molecules (such as cytokines) prepared synthetically or that are not produced by the patients themselves is called as passive immunotherapy. Conversely, a vaccine is a form of active immune therapy because it elicits an immune response in patients. A cancer vaccine may be made of whole tumor cell or of substances or fragments contained in the tumor called antigens.
Newer types of immunologic therapy that are still considered investigational as of 2003 include cell-based therapies. Instead of using synthetic chemicals that resemble substances produced by the body, cell-based therapies use modified stem cells or dendritic cells as vaccines against cancer. Stem cells are undifferentiated cells whose daughter cells can develop into various types of specialized cells, while dendritic cells are cells that are able to initiate and modify the immune system's responses to cancer by activating B cells and T cells. Dendritic cells appear to offer a promising new form of immunotherapy for cancer.
Another investigational form of treatment is the development of cell-free tumor-specific peptide vaccines. Peptides are subunits of protein molecules that contain two or more amino acids. Peptide vaccines are intended to induce responses in the patient's T cells that inhibit tumor growth. As of late 2003, however, peptide-based tumor vaccines have been shown to shrink cancerous tumors only in patients with limited disease.

Adoptive immunotherapy

Adoptive immunotherapy involves stimulating T lymphocytes by exposing them to tumor antigens. These modified cells are grown in the laboratory and then injected into patients. Since the cells taken from a different individual for this purpose often results in rejection, patients serve both as donor and recipient of their own T cells. Adoptive immunotherapy is particularly effective in patients who have received massive doses of radiation and chemotherapy. In such patients, therapy results in immunosup-pression (weakened immune systems), making them vulnerable to viral infections. For example, CMV-specific T cells can reduce the risk of cytomegalovirus (CMV) infection in transplant patients.

Resources

Periodicals

Fishman, M. N., and S. J. Antonia. "Cell-Based Immune Therapy for Metastatic Renal Cancer." Expert Review of Anticancer Therapy 3 (December 2003): 837-849.
"Immunoprevention of Cancer: Is the time Ripe?" Cancer Research 60 (May 15, 2000): 2571-2575.
National Cancer Institute. Treating Cancer with Vaccine Therapy. June 29, 2001. 〈http://cancertrials.nci.nih.gov/news/features/vaccine/html/page05.htm 2000〉.
Nieda, M., M. Tomiyama, and K. Egawa. "Ex vivo Enhancement of Antigen-Presenting Function of Dendritic Cells and Its Application for DC-Based Immunotherapy." Human Cell 16 (December 2003): 199-204.
Paczesny, S., H. Ueno, J. Fay, et al. "Dendritic Cells as Vectors for Immunotherapy of Cancer." Seminars in Cancer Biology 13 (December 2003): 439-447.
Rosenberg, S. A. "Progress in Human Tumor Immunology and Immunotherapy." Nature 411, no. 6835 (2001): 380-385.
Scheibenbogen, C., A. Letsch, A. Schmittel, et al. "Rational Peptide-Based Tumour Vaccine Development and T Cell Monitoring." Seminars in Cancer Biology 13 (December 2003): 423-429.

Key terms

AIDS — Acquired immune deficiency syndrome. A disease caused by infection with the human immunodeficiency virus (HIV). In people with this disease, the immune system breaks down, increasing vulnerability to other infections and some types of cancer.
Bone marrow — Soft tissue that fills the hollow centers of bones. Blood cells and platelets (disk-shaped bodies in the blood that are important in clotting) are produced in the bone marrow.
Chemotherapy — Treatment of an illness with chemical agents. The term usually is used to describe the treatment of cancer with drugs.
Clot — A hard mass that forms when blood coagulates.
Fetus — A developing baby inside the womb.
Hepatitis — Inflammation of the liver caused by a virus, chemical, or drug.
Immune response — The body's natural protective reaction to disease and infection.
Immune system — The system that protects the body against disease and infection through immune responses.
Inflammation — Pain, redness, swelling, and heat that usually develop in response to injury or illness.
Psoriasis — A skin disease that manifests itself with itchy, scaly, red patches on the skin.
Seizure — A sudden attack, spasm, or convulsion.
Shingles — A disease caused by an infection with the Herpes zoster virus—the same virus that causes chickenpox. Symptoms of shingles include pain and blisters along one nerve, usually on the face, chest, stomach, or back.
Sickle cell anemia — An inherited disorder in which red blood cells contain an abnormal form of hemoglobin, a protein that carries oxygen. The abnormal form of hemoglobin causes the red cells to become sickle-shaped. The misshapen cells may clog blood vessels, preventing oxygen from reaching tissues and leading to pain, blood clots and other problems. Sickle cell anemia is most common in people of African descent and in people from Italy, Greece, India, and the Middle East.
References in periodicals archive ?
Kunkel brings extensive experience in developing and commercializing oncologic and immunologic therapies, with over 20 years of executive responsibilities in industry including clinical, regulatory, medical affairs and licensing.
The immunologic therapies that were assessed included agents such as immunoglobulin, Ampligen(R), Acyclovir, Interferon, and transfer factor.
Alternative therapies for patients with a CFS diagnosis have included: vitamins; coenzymes; minerals and other nutritional approaches; herbal remedies; homeopathy; naturopathy; anticardidal treatment; traditional Chinese medicine, including acupuncture, moxibustion, Chinese herbs and Qi Gong; Ayurvedic medicines; meditation and relaxation; detoxification therapies; and unproved immunologic therapies (Anderson & Ferrans, 1997; Berne, 1995; Feiden, 1990; Kantrowitz et al.
Many newer immunologic therapies are under investigation, including intravenous immunoglobulins.