Definition of 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,is a type of treatment that works with human’s immune system. It can help fight cancer or help control side effects from other cancer treatments like chemotherapy.
Biological therapy and chemotherapy are both treatments that fight cancer. While they may seem alike, they work in different ways. Biological therapy helps body’s immune system fight cancer. Chemotherapy attacks the cancer cells directly.
Biological therapy helps body’s immune system fight cancer with following ways:
• Stop or slow the growth of cancer cells.
• Make it easier for your immune system to destroy, or get rid of, cancer cells.
• Keep cancer from spreading to other parts of your body.
Body’s immune system and its function
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 work 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.
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Tumor-associated antigens are additionally expressed on the tumor cell surface |
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Antigens and antibodies |
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Antibody structure with antigen-binding site |
Body’s immune system includes your spleen, lymph nodes, tonsils, bone marrow, and white blood cells. The following cells help protect body from getting infections and diseases.
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.
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Process of B cell lymphocyte maturation. |
Role of the B cell in the immune response to malignant disease |
• 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.
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Process of B cell lymphocyte maturation. |
T cell activity in the immune response to malignant disease. Helper T cells (Th MHC class II restricted) mediate effects by secretion of cytokines to activate other cells. Cytotoxic T cells (Tc HC class I restricted) medi |
• 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.
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Scanning electron microscopic view of peripheral blood leukocytes. (B, B cell; M, macrophage; T, T cell; Int., intermediate form, which may be of the “double cell” variety) |
• 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.
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| Macrophage role in the immune response to malignant disease. |
Development of effector cells within the immune system. Th, Ts, and NK lymphocytes require cytokine activation to differentiate into LAK cells |
Biological response modifiers and their use for 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.
BRMs 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.
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.
As to interferons
Interferons (IFNs) were the first cytokines produced in the laboratory for use as BRMs. They are types of cytokines that occur naturally in the body. 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.
It is proved 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. Some interferons may also stimulate NK cells, T cells, and macrophages, boosting the immune system’s anticancer function.
Interferon alpha has been approved in many countries for the treatment of certain types of cancer, including hairy cell leukemia, melanoma, chronic myeloid leukemia, and AIDS-related Kaposi’s sarcoma.Interferon alpha may also be effective in treating other cancers such as kidney cancer and non-Hodgkin’s lymphoma. It was showed that combinations of interferon alpha and other BRMs or chemotherapy can effectively treat a number of cancers.
As to interleukins
Interleukins (ILs) are also cytokines that occur naturally in the body and can be made in the laboratory. Interleukin-2 (IL–2) 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. It is proved that IL–2 has been valuable for the treatment of metastatic kidney cancer and metastatic melanoma.
Benefits of interleukins to treat a number of other cancers, including leukemia, lymphoma, and brain, colorectal, ovarian, breast, and prostate cancers,have been studied.
As to 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.
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. Therefore, CSFs are particularly useful when combined with high-dose chemotherapy.
Some 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 (epoiten) can increase the number of red blood cells and reduce the need for red blood cell transfusions in patients receiving chemotherapy; and
• Interleukin-11 (oprelvekin) helps the body make platelets and can reduce the need for platelet transfusions in patients receiving chemotherapy.
Researchers are studying CSFs in clinical trials to treat a large variety of cancers, including lymphoma, leukemia, multiple myeloma, melanoma, and cancers of the brain, lung, esophagus, breast, uterus, ovary, prostate, kidney, colon, and rectum.
As to monoclonal antibodies
The effectiveness of certain antibodies made in the laboratory called monoclonal antibodies (MOABs or MoABs) are evaluated. These antibodies are produced by a single type of cell and are specific for a particular antigen.
To create MOABs, scientists first inject human cancer cells into mice. In response, the mouse immune system makes antibodies against these cancer cells. The scientists then remove the mouse plasma cells that produce antibodies, and fuse them with laboratory-grown cells to create “hybrid” cells called hybridomas. Hybridomas can indefinitely produce large quantities of these pure antibodies, or MOABs.
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Monoclonal antibodies antibodies can be made to recognize and attach to unique proteins on the surface of cancer cells. After the cancer cell is coated with antibodies, cells of the immune system recognize and destroy the |
There are a number of ways by which MOABs may be used to treat cancer:
• 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 carrying radioisotopes may also prove useful in diagnosing certain cancers, such as colorectal, ovarian, and prostate.
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Radioactive particles can be attached to monoclonal antibodies. The antibodies carry the particles to cancer cells, where the radioactive material is then concentrated to kill the neoplastic cells |
Rituxan® (rituximab) and Herceptin? (trastuzumab) are examples of MOABs that have been approved by the FDA.
• Rituxan is used for the treatment of non-Hodgkin’s lymphoma.
• Herceptin is used to treat metastatic breast cancer in patients with tumors that produce excess amounts of a protein called HER–2.
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A, The drug-laden antibody attaches to the cancer cell’s surface. B, The drugs or toxins-although not necessarily the antibody-are engulfed by the cell. C, When inside the cell, the drugs or toxins poison the cell. One toxi |
In clinical trials, researchers are testing MOABs to treat lymphoma, leukemia, melanoma, and cancers of the brain, breast, lung, kidney, colon, rectum, ovary, prostate, and other areas.
As to cancer vaccines
Cancer vaccines are another form of biological therapy currently under study. Vaccines for infectious diseases, such as measles, mumps, and tetanus, are injected into a person before the disease develops. These vaccines 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 system to increase production of plasma cells that make antibodies specific to the infectious agent. The immune system also increases production of T cells that recognize the infectious agent. These activated immune cells remember the exposure, so that the next time the agent enters the body, the immune system is already prepared to respond and stop the infection.
Cancer vaccines may encourage the patient’s immune system to recognize cancer cells. They are designed to treat existing cancers (therapeutic vaccines) or to prevent the development of cancer (prophylactic vaccines). Therapeutic vaccines are injected in a person after cancer is diagnosed. These vaccines may stop the growth of existing tumors, prevent cancer from recurring, or eliminate cancer cells not killed by prior treatments. Cancer vaccines given when the tumor is small may be able to eradicate the cancer. On the other hand, prophylactic vaccines are given to healthy individuals before cancer develops. These vaccines are designed to stimulate the immune system to attack viruses that can cause cancer and to prevent the development of certain cancers.
Early cancer vaccine clinical trials involved mainly patients with melanoma. Therapeutic vaccines are also being studied in the treatment of many other types of cancer, including lymphoma, leukemia, and cancers of the brain, breast, lung, kidney, ovary, prostate, pancreas, colon, and rectum. Researchers are also studying prophylactic vaccines to prevent cancers of the cervix and liver. Moreover, scientists are investigating ways that cancer vaccines can be used in combination with other BRMs.
Dendritic Cell (DC) Therapy or so-called Dendritic Cell vaccine is a newly emerging and potent form of immune therapy used to treat cancer, AIDS and other serious conditions. In case of cancer, Dendritic Cell therapy is an immune therapy which harnesses the body's own immune system to fight cancer. The Dendritic Cell itself is an immune cell whose role is the recognition, processing and presentation of foreign antigens to the T-cells in the effector arm of the immune system. Although Dendritic Cells are potent cells, they are not usually present in adequate quantity to allow for a potent immune response. Dendritic Cell Therapy thus involves the harvesting of blood cells (ie monocytes or macrophages) from a patient and processing them in the laboratory to produce Dendritic Cells which are then given back to a patient in order to allow massive Dendritic participation in optimally activating the immune system. To learn more about vaccine and Dendritic Cell therapy for cancer, please read the following articles “Dendritic Cell vaccine therapy”.
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Future clinical trials with dendritic cells pulsed with tumor epitopes derived from newly identified tumor-associated peptides, RNA, lystates, and apoptotic bodies. Dendritic cells might also be genetically modified with |
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