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Immunotherapy
Immunotherapy is an array of treatment strategies based upon the concept of modulating the immune system to achieve prevention and/or therapeutic goal. As evidence of immune system involvement in the development of multiple sclerosis (MS) has grown, trials of various new treatments to alter or suppress immune response are being conducted. Most of these therapies are, at this time, still considered experimental.

Clinical trials have shown that immunosuppressive agents and techniques can positively affect the course of MS, at least while remaining on those treatments. On the down side, generalized immunosuppression leaves the patient open to a variety of viral, bacterial, and fungal infections.

The immune system is a complicated network of cells and organs. The bone marrow, thymus gland, spleen and lymph nodes work together to defend the body against attacks by "foreign" invaders. The immune system is the body's main defense again infection and disease. The immune system can work against diseases, including MS, in several ways. The immune system may recognize the difference between healthy cells and cancer cells for instance, in the body and work to get rid of the cancer cells. However, the immune system can't always recognize cancer cells as "foreign".

Immunotherapy works on the immune system in various ways by repairing, stimulating or enhancing the immune system's responses.

Over the years, MS investigators have studied a number of immunosuppressant treatments. One such treatment, Novantrone (mitoxantrone), was approved by the U.S. Food and Drug Administration (FDA) for the treatment of advanced or chronic MS. Other therapies being studied are cyclosporine (Sandimmune), cyclophosphamide (Cytoxan), methotrexate, azathioprine (Imuran), and total lymphoid irradiation. Lymphoid irradiation is a process whereby the MS patient's lymph nodes are irradiated with x-rays in small doses over a few weeks to destroy lymphoid tissue, which is actively involved in tissue destruction in autoimmune diseases.

Inconclusive and/or contradictory results of these trials along with the potentially dangerous side effects, show the need that further research is necessary to determine what, if any, role they should play in the management of MS. Studies are also being conducted with the immune system modulating drug cladribine (Leustatin).

Another potential treatment for MS is monoclonal antibodies (MAB or MoAb), which are identical, laboratory-produced antibodies that are highly specific for a single antigen. They are injected into the patient in the hope that they will alter the patient's immune response. One monoclonal antibodies is natalizumab (Tysabri) which was shown in clinical trials to significantly reduce the frequency of attacks in people with relapsing forms of MS and was approved for marketing by the FDA in 2004. Regarding MS, Tysabri is believed to work by reducing the ability of inflammatory immune cells to attach to and pass through the cell layers lining the blood-brain barrier.

Another experimental treatment for MS is plasma exchange, or plasmapheresis. Plasmapheresis is a procedure in which blood is removed from the patient and the blood plasma is separated from other blood substances that may contain antibodies and other immunologically active products. These other blood substances are discarded and the plasma is then transfused back into the patient. Because its worth as a treatment for MS hasn't been proven, this experimental treatment remains at the stage of clinical testing.

Bone marrow transplantation which is a procedure in which bone marrow from a healthy donor is infused into patients who have undergone drug or radiation therapy to suppress their immune system so they will not reject the donated marrow. Injections of venom from honey bees are also being studied. Each of these therapies carries the risk of potentially severe side effects.

Immunosuppression

This is the natural or induced active suppression of the immune response, as contrasted with deficiency or absence of components of the immune system. Like many other complex biological processes, the immune response is controlled by a series of regulatory factors.

A variety of suppressor cells play a role in essentially all of the known immunoregulatory mechanisms, such as maintenance of immunological tolerance; limitation of antibody response to antigens of both thymic-dependent and thymic-independent types, as well as to antigens that stimulate reaginic antibody (antibodies involved in allergic reactions); genetic control of the immune response; idiotype suppression; control of contact and delayed hypersensitivity; and antigenic competition.

Some portions of the immune system itself have immunosuppressive effects on other parts of the immune system, and immunosuppression may occur as an adverse reaction to treatment of other conditions.

Suppression of the immune response may be specific to a particular antigen or may be a response to a wide range of antigens encountered. The whole immune response may be depressed, or a particular population of immunologically active lymphocytes may be selectively affected. In some cases, the effect may be greater on T lymphocytes (T cells) rather than B lymphocytes (B cells). If B cells are affected, it may be on a specific subclass of antibody-producing cells. Antigen-specific immunosuppression may be the result of deletion or suppression of a particular clone of antigen-specific cells, or the result of enhanced regulation of the immune response by antigen-specific suppressor cells. It can also be the result of increased production of antiidiotypic antibody.

The result of any immune response is a balance between the action of effector cells mediating the phenomenon and suppressor cells regulating the response. Anything that reduces the regulatory function of suppressor cells will functionally increase the immune response. As suppressor cells are derived from rapidly turning-over precursor cells, and effector cells of T cell-mediated immunity are derived from slowly dividing precursors, it's possible preferentially to depress the action of suppressor cells without affecting effector cells. This may be done by the use of alkylating agents such as cyclophosphamide given before immunization. Cyclophosphamide used in this way can increase a normal cell-mediated immune response, reverse immunological tolerance caused by increased regulatory activity of suppressor cells, and even reverse antigenic competition.

Immunocompromised or Immunodeficiency

This is a group of disorders in which part of the immune system is missing or defective. Because of this, the body's ability to fight infections is impaired (compromised) or entirely absent. As a result, a person with an immunodeficiency disorder will have frequent infections that are generally more severe and last longer than usual.

The 2 main types of immunodeficiency disorders are congenital immunodeficiency (also called primary immunodeficiency) and acquired immunodeficiency. This is also discussed in greater detail in the Immune Disorders section of this site.

Congenital immunodeficiency is present at the time of birth, and is the result of mainly genetic defects. Even though more than 70 different types of congenital immunodeficiency disorders have been identified, they rarely occur. Congenital immunodeficiencies may occur as a result of defects in B cells, T cells, or both. They can also occur in the innate immune system.

Acquired immunodeficiency is more common than congenital immunodeficiency. It's the result of an infectious process or other disease. For example, the human immunodeficiency virus (HIV) is the virus that causes acquired immunodeficiency syndrome (AIDS). Sometimes it can be brought on by drugs used to treat another condition.

Immunosuppressive Agents

These are drugs that inhibit or prevent activity of the immune system. They are used in immunosuppressive therapy to treat autoimmune diseases or diseases that are most likely of autoimmune origin such as MS. These drugs, however, carry side-effects and risks with them. Because the majority of them act non-selectively, the immune system is less able to resist infections.

Examples have included the use of azathioprine (Imuran), methotrexate (Rheumatrex), cyclophosphamide (Cytoxan), cyclosporin (Sandimmune), cladribine (Leustatin), mitoxantrone (Novantrone), total lymphoid radiation, monoclonal antibodies, corticosteroids, intravenous gammaglobulin, plasma exchange and bone marrow transplants.

The clinical success rate for these approaches to the management of MS patients has been disappointing. The use of these drugs has remained limited and should be considered only in very selected circumstances.

Immunomodulating Agents

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.

Examples of immunomodulating agents are Avonex, Betaseron, Copaxone, Rebif and Extavia. The clinical success rate has been good and the use of these types of drugs has proven useful especially in the early stages of the disease.
Immunotherapy Examples
Biological response modifiers (BRMs) are substances that stimulate the body's response to infection and disease. The body naturally produces small amounts of these substances. Some antibodies, cytokines (proteins secreted by cells of the immune system) and other immune system substances can be produced in the laboratory for use in cancer treatment. They alter the interaction between the body’s immune defenses and cancer cells to boost, direct, or restore the body's ability to fight disease. Examples of BRMs include Interferons, interleukins, colony stimulating factors, monoclonal antibodies, vaccines, gene therapy, and non specific immunomodulating agents.

Interferons

Interferons (IFNs) are a group of proteins called cytokines produced by white blood cells, fibroblasts, or T cells as part of an immune response to a viral infection or other immune trigger. The name of the proteins comes from their ability to interfere with the production of new virus particles.

There are three types of interferons: Alfa, beta, and gamma. Alfa and beta interferons, which are grouped together as type I interferon, are produced by white blood cells and a type of connective tissue cell called a fibroblast. Gamma interferon, or type II interferon, is manufactured T cells. Production occurs when the T cells are activated such as during an infection.

Interferon alpha (IFN-α) proteins are produced by leukocytes and are mainly involved in innate immune responses against viral infection.

Interferon beta (IFN-β) proteins are produced by fibroblasts and are mainly involved in innate immune responses. The type most widely used in MS treatment.

Interferon gamma (IFN-γ) , also known as immune interferon, it has antiviral, immunoregulatory, and anti-tumor properties.

Interleukins

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 has been the most widely studied in cancer treatment. Interleukin-2 stimulates the growth and activity of many immune cells such as lymphocytes.

Colony-Stimulating Factors (SF)

Colony-stimulating factors sometimes called hematopoietic growth factors, usually don't 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.

Colony-stimulating factor's 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 decrease the risk of infection or the need for transfusion with blood products, due to chemotherapy treatment.

Monoclonal Antibodies (MAb or MoAb)

Monoclonal antibodies are monospecific antibodies that are the same because they are made by one type of immune cell which are all clones of a unique parent cell. Given almost any substance, it's possible to create monoclonal antibodies that specifically bind to that substance; they can then serve to detect or purify that substance. These antibodies are produced by a single type of cell and are specific for a particular antigen.

Monoclonal antibodies are currently the most widely used form of cancer immunotherapy.

Some ways that monoclonal antibodies are used in cancer treatment:

Monoclonal antibodies that react with specific types of cancer may enhance a patient's immune response to the cancer.

Monoclonal antibodies can be programmed to act against cell growth factors, thus interfering with the growth of cancer cells.

Monoclonal antibodies may be linked to anticancer drugs, radioisotopes, other BMRs or other toxins. When the antibodies latch onto cancer cells, they deliver these poisons directly to the tumor, helping to destroy it.

Gene Therapy

Gene therapy is an experimental treatment that involves introducing genetic material into a person's cells to fight disease. Researchers are studying gene therapy methods that can improve a patient's ability to recognize and attack cancer cells. In another approach, scientists inject cancer cells with genes that cause the cancer cells to produce cytokines and stimulate the immune system. A number of clinical trials are currently studying gene therapy and its possible application to the treatment of cancer.

Side Effects of Biological Therapies

Like any form of treatment biological therapies can cause a number of side effects, which can vary widely from agent to agent and 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 some BRMs. Blood pressure may also be affected. The side effects of interleukin 2 can often be severe, depending on the dosage given. Patients need to be closely monitored during treatment with high doses of interleukin 2. Side effects of colony stimulating factors may include bone pain, fatigue, fever, and appetite loss. The side effects of monoclonal antibodies vary, and serious allergic reactions may occur.